The world number one cruised in the opening set, before Hurkacz put up more of a fight in the second.
Djokovic eventually prevailed to seal a 6-3 7-5 win, successfully seeing off his opponent despite Hurkacz valiantly throwing everything at him.
The 35-year-old Serbian has now won 15 consecutive matches in 2023, with his latest impressive display including just seven unforced errors, less than half Hurkacz's 15 as Djokovic's clinical edge proved decisive.
Fifteen successive victories is the fourth-best start to a season in Djokovic's career, though he remains some way off the 41-0 record he began 2011 with.
A semi-final clash against Daniil Medvedev awaits following the Russian's comfortable 6-3 6-2 victory against Borna Coric, which clocked in at one hour and 21 minutes.
Medvedev is also in the midst of an impressive winning streak, rattling off 12 consecutive successes since being eliminated by Sebastian Korda at the Australian Open in January.
Andrey Rublev booked his spot in the final four with a 6-3 7-6 (7-3) victory over Botic van de Zandschulp to maintain his title defence.
He will face seventh seed Alexander Zverev in the semi-final, the German having seen off Lorenzo Sonego 7-5 6-4.
Djokovic, who is celebrating a record 378th week as world number one, had to rely on a third-set tie-break to finally get over the line, defeating his Czech opponent 6-3 3-6 7-6 (7-1) on Tuesday.
Machac is ranked 130th in the world, but caused Djokovic plenty of problems, earning 10 break points across the match, though he was only able to convert three.
Djokovic had a 4-1 lead in the deciding set before Machac fought back to force a tie-break, but the Australian Open champion ultimately had few problems at 6-6 as he won seven of the eight points played to clinch the win.
"Tomas certainly didn't play like the No. 130 in the world today," Djokovic said of his opponent. "He was giving me all kinds of trouble. But I guess when it mattered, I found another gear."
Djokovic, who is still undefeated in 2023, will face Tallon Griekspoor in the second round.
Elsewhere, fresh off two titles in as many weeks, third seed Daniil Medvedev eased past Matteo Arnaldi 6-4 6-2 to tee up a tie with Alexander Bublik next after his opponent Alexandar Lazarov retired hurt with Bublik leading 6-1 1-0.
Felix Auger-Aliassime defeated Maxime Cressy 7-6 (7-4) 3-6 6-3, but sixth seed Karen Khachanov is out after he was beaten 7-5 6-2 by Botic van de Zandschulp.
The Dutchman will take on Mikael Ymer in the second round after his 6-2 6-3 win against Francesco Passaro, while eighth seed Borna Coric and Dan Evans played just four games before the latter retired hurt.
Christopher O'Connell set up a match against Alexander Zverev in the next round after he overcame Emil Ruusuvuori 7-5 6-4.
The men's world number one has not played a competitive match since early December and was last month deported from Australia on the eve of the Australian Open.
That decision was a result of Djokovic opting not to join the majority of his tennis peers in getting vaccinated against COVID-19 and amid controversy over how he handled getting the virus himself in December.
Speaking to the BBC in a recent interview, Djokovic stated he was prioritising his right to choose what to put into his body above his sporting ambitions and confirmed he is willing to miss further grand slams if necessary.
With COVID restrictions still in place in many countries, Djokovic acknowledges his options to play are limited.
"I just have to follow the rules. You know, whatever tournament that I'm able to play, I will be trying to get to that country and play the tournament," Djokovic said ahead of facing Lorenzo Musetti in round one of the Dubai Tennis Championships.
"Obviously, I'm not intending to play the full schedule and that wasn't also my intention, as you brought it up and my goal prior to this season or the season before, and I was trying to aim to play my best at the grand slams and some of the 1000 events we have, of course, and playing for my country, those were the biggest motivations that I had in terms of the scheduling.
"Right now, the situation is obviously different for me. So, I really can't choose right now. It's really about where I can go and play. So, wherever I have an opportunity, I'll be using probably that opportunity and going to play because this is what I do, it's what I love to do still.
"And I have support from my family and my team is still there with me and that's what's important for me because obviously it was not easy for anyone in my surroundings to go through these kinds of circumstances and situations that we have been through.
"But it's very exciting to have everyone together here with me. And in Dubai, we're back on the tour and then we'll play this tournament and we'll see how it goes further down the line."
Several stars backed the decision for Djokovic to be barred from playing in Melbourne, with most noting that he had not followed the rules in order to do so.
But the Serbian says he has been received warmly ahead of his return to the ATP Tour.
"I haven't seen too many players, but the players that I've seen have been positive and welcoming," he added.
"And it's nice to see obviously. I can't say that was the case in Australia. It was a little bit strange, but here it's well so far."
Djokovic's 86-week reign at the top of the ATP rankings will end on Monday, after the Serbian lost to qualifier Jiri Vesely 6-4 7-6 (7-4) in the Dubai Tennis Championships.
That means that Daniil Medvedev will leapfrog Djokovic regardless of whether or not he wins in Acapulco.
Using his official Twitter account, Djokovic congratulated both Vesely – who won his only previous meeting with the 20-time grand slam champion back in 2016 – and Medvedev.
"Well played @jiri_vesely, that was a great game. Wish you the best of luck for the rest of the tournament," Djokovic wrote, accompanying his post with a thumbs up emoji.
"Congratulations also to a very deserving @DaniilMedwed, who will now become world number one."
His appearance in Dubai was Djokovic's first competitive action of 2022, after he was unable to feature at the Australian Open due to his refusal to be vaccinated against COVID-19.
While suggesting he is still working his way back to full sharpness after not playing since December, Djokovic insisted he is fully motivated to carry on playing.
"My goal is to keep on playing tennis," Djokovic said in his post-match news conference.
"That's the ultimate goal. For as long as I really feel like it and as long as I can play. As long as my body allows me, as long as the circumstances in my life as well, the people that surround me [and] support me.
"I'm still motivated and I'm still p***** off when I lose a match. I care about it. I care about winning every match, as anybody else on the Tour, regardless of the age. I'm actually glad that I'm feeling a lot of emotions every single day because it means that I really want to be part of this sport, part of the Tour.
"Unfortunately, [it] wasn't my day. I congratulate Jiri. He played better.
"The more matches I play, the more comfortable I get on the court. I need the match play. I didn't have many matches at all last few months.
"I don't look at the age really as a restricting factor for my career. I still feel great in terms of my body and the way it's holding on, the way it's recovering. It's been serving me well, so to say. That's something that obviously encourages me to keep going."
After dominating his first-round encounter against Malek Jaziri in one hour, Djokovic won a similarly straightforward contest with Philipp Kohlschreiber 6-3 6-1 in just 59 minutes on Wednesday.
In the build-up, Djokovic had pointed to his loss against Kohlschreiber at Indian Wells last year on the previous occasion they had met on a hard court as evidence he was facing a big test.
But the Serbian triumphed without facing a break point, hitting 23 winners and just 10 unforced errors in improving his 2020 record to 15-0.
Khachanov, who has won one of his three meetings with Djokovic, moved through after seeing off Dennis Novak 6-3 6-4.
"I've had some interesting battles with him," Djokovic said of Khachanov. "He is a great guy, a very powerful player.
"He is one of the guys who is a pretender to be top five, top 10. He is very dedicated, so hopefully I'll be as sharp as I have been in the past two matches and start well."
Djokovic felt he had barely put a foot wrong against Kohlschreiber, who at 36-years-old is now ranked at number 80.
"It was a great performance," said the Australian Open champion. "I enjoyed the way I played, coming out with the right focus and tactics.
"Knowing Philipp beat me 12 months ago in Indian Wells, I needed to approach this match very seriously regardless of his ranking."
Second seed Stefanos Tsitsipas joined Djokovic in the quarter-finals at the ATP 500 event, beating Alexander Bublik – a player he also got the better of en route to Open 13 Marseille glory last week - 7-6 (7-1) 6-4.
Tsitsipas will now play Jan-Lennard Struff, who defeated Nikoloz Basilashvili.
Andrey Rublev saw off Filip Krajinovic 7-6 (7-3) 6-0 to book a clash with Dan Evans, who was on the brink of elimination but saved three match points in a thriller against Pierre-Hugues Herbert, eventually winning 7-5 3-6 7-6 (9-7).
Richard Gasquet eliminated fellow Frenchman and eighth seed Benoit Paire 6-4 6-4, while in-form Gael Monfils was a comfortable 6-1 6-2 winner over Yasutaka Uchiyama.
Djokovic, who last month won the Australian Open to move level with Rafael Nadal on 22 grand slam titles, has not played since claiming the title in Melbourne.
The world number one was nursing a hamstring issue throughout the season's first major, but he confirmed at a press conference in Belgrade on Wednesday that he will return to action at the Dubai Tennis Championships next week.
Djokovic could not compete in the United States last season due to his COVID-19 vaccination status, though his brother Djordje has claimed the 35-year-old has applied for a "special permit" to enter the country.
He has received clearance from the tournament organisers to play at the two Masters 1000 events at Indian Wells and in Miami but now faces a wait to find out if the U.S. government will grant him entry.
"The process for that has started. It is out of my control now," Djokovic said.
"I'd love to play and I'm glad I received the approval of directors in Miami and Indian Wells. I hope the decision makers will give the approval."
On his progress on the injury front, Djokovic explained: "As for the injury I sustained at the Australian Open, it's healed, but I'm not 100 per cent yet.
"Things are looking very good. As a team, we made the decision to go to Dubai."
Djokovic has won the Dubai Tennis Championships five times, though the last of those titles came in 2020.
He was knocked out by Jiri Vesely in the quarter-finals last year.
Djokovic this week tied Steffi Graf on 377 weeks spent as world number one.
The outright record is set to become his next week, with Carlos Alcaraz unable to surpass him even if the young Spaniard wins the Rio Open.
At the age of 27, and with little warning, Karatsev has hurtled from obscurity before tennis went into lockdown 12 months ago to real prominence.
A 6-3 6-2 victory over South African Lloyd Harris on Saturday gave him a trophy for his efforts and he will enter the top 30 on Monday, having never had a double-digit ranking before this season.
Karatsev reached the Australian Open semi-finals last month, having had to win three qualifying rounds to make the main draw, and it took Novak Djokovic to stop that charge in Melbourne.
Now Vladikavkaz-born Karatsev is back in another winning routine, with Andrey Rublev, Jannik Sinner and Dan Evans having figured among his victims en route to the Dubai final.
The first-time champion said on Amazon Prime: "I am super happy. It was a tight match. [I was] really nervous. I want to congratulate my opponent for the final [run]. He did a great week. Every final is different, so I am happy that I won."
Karatsev had some promising results at Challenger Tour level last year but had never shown form on the main circuit until the start of 2021, and suddenly he looks a major force to be reckoned with.
He said of the rush of success: "You never know when it is coming. I did a good job with my team, with my coach and it has happened now."
After 14 months out following knee surgery, Federer was back in action at the Qatar Open on Wednesday, defeating friend and practice partner Dan Evans in three sets in the last 16.
But Nikoloz Basilashvili, Federer's next opponent, proved a step too far in the quarter-finals on Thursday as the 39-year-old Swiss superstar went down 3-6 6-1 7-5.
Federer breezed through the opener and recovered from a tough second set to forge a match point in the decider, but Basilashvili stuck with his "idol" and earned a first career win against the 20-time grand slam champion.
The result would not put a dampener on Federer's week, however.
"I'm already over it," Federer said. "I mean I would have loved to play tomorrow - don't get me wrong, you know - but at the same time I'm also happy to get a rest.
"I'm happy how I played today. I'm happy how I did yesterday. I'm happy I was back on the Tour. I'm pleased I came here to Doha.
"So it's a really, really positive return for me.
"I'm actually happy that I was able to play back-to-back three-set matches against top players. That's an important step forward for me. This is a stepping stone."
But Federer announced later on Thursday he had made the decision to return to training, putting on hold plans for a second tournament of the season.
He had been set to join a number of other big names in Dubai, although Spanish great Rafael Nadal has rejected a wildcard.
Federer wrote on his social media pages: "It's been great to be back on the @atptour, loved every minute playing in Doha once again. A big thank you to the best and loyal team that helped me get here.
"I've decided it's best to go back to training and as a result, I've decided to withdraw from Dubai next week."
Federer is an eight-time Dubai champion, most recently in 2019 when he defeated Stefanos Tsitsipas in the final.
A series of upsets meant Jabeur was the only seed left in the tournament going into Thursday, but she was outfought by Halep, whose win-loss record in 2022 now stands at 11-1.
The result followed two years on from Halep beating Jabeur in the second round at the same tournament, on that occasion needing a third-set tie-break to get the better of the Tunisia. Halep went on to win the title on that occasion.
"It was a very tough match. Even if it's in two sets, it felt much harder than that," Halep said of Thursday's win.
"I had in my mind big time the match from 2020, it was so close and I knew I'd have to fight till the end."
Quoted on the WTA website, former Wimbledon and French Open winner Halep added: "I've been focused on what I have to do, and I wanted just to push Jabeur back because she has such a big game."
Halep will face Jelena Ostapenko in the last four after the big-hitting Latvian overcame Petra Kvitova 5-7 7-5 7-6 (11-9).
Kvitova led by a set and a break, and twice served for the match, yet Ostapenko prevailed to add the 2013 Dubai champion to the scalps of Sofia Kenin and Iga Swiatek this week.
Ostapenko, who triumphed in two hours and 39 minutes, has now reached at least the semi-finals in four of her last seven tournaments.
The other semi-final will be contested by Veronika Kudermetova and Marketa Vondrousova.
Kudermetova reached her third career WTA 500 semi-final after beating lucky loser Jil Teichmann 6-2 5-7 6-4 in two hours and 23 minutes.
Vondrousova, meanwhile, became just the third ever qualifier to reach the last four of the tournament thanks to a 7-5 6-4 win over Dayana Yastremska.
Halep, appearing for the first time since a run to the last four at the Australian Open, lost to Sabalenka in their most recent meeting - in Adelaide in January - but had won her prior two encounters with the world number 13.
Despite trailing in the first set, the world number two rallied in the second thanks to three breaks of serve, before cruising in the decider to wrap up a 3-6 6-2 6-2 win over her Belarusian opponent.
The Romanian, a Dubai champion in 2015, will now go up against Jennifer Brady, whose run of upsets continued as she overcame Australian Open finalist Garbine Muguruza to claim her third straight top-20 triumph.
Having already knocked out third seed Elina Svitolina and Marketa Vondrousova in previous rounds, Brady moved into the semis with a 6-7 (5-7) 6-3 6-4 win.
It is the first time in Brady's career that the American has made it into the last four of a WTA Premier event, though she was not fully satisfied with her performance.
"I wasn't feeling my best," she said in quotes reported by the WTA's official website. "Maybe I didn't play my best tennis, but I just found a way to stay in there, compete and come out on top."
The other semi-final will see Elena Rybakina, whose fine run continued with a win over Karolina Pliskova, meet Petra Martic.
Dubai debutant Rybakina has started 2020 in fine form and dispatched world number three Pliskova on Thursday, completing a 7-6 (7-1) 6-3 success in one hour and 41 minutes.
It means Rybakina has made her fourth semi-final in five tournaments so far this year, with a tie against Martic - who beat Anett Kontaveit 7-6 (7-4) 6-1 - her reward.
Top seed Halep came through a testing quarter-final with Aryna Sabalenka, but her last-four match was significantly more straightforward on Friday.
Halep blitzed through the encounter in just 62 minutes, the 2015 champion appearing way more at ease than in the pair's first-round clash at the Australian Open in January, when Brady succumbed 7-6 (7-5) 6-1.
World number two and two-time grand slam champion Halep faced only two break points in the entire match and she saved both, while she also hit 16 winners to eight unforced errors in a performance she felt was almost perfect.
"It's fun when you feel the ball and when you can do anything you want," Halep said. "Today it was one of those days, I could open the court easily. I felt like every time I hit the ball, I feel it.
"It's always a nice opportunity and privilege to play the last match of the tournament. I play for another trophy, so I'm relaxed. I'm focused. I really want it."
Elena Rybakina will be Halep's next opponent, with the Kazakh securing progress to a fourth final already this year.
Rybakina showed her resilience to come through a gripping duel with eighth seed Petra Martic, saving set points in both sets before eventually winning 7-6 (7-5) 7-6 (7-2).
The 20-year-old has already beaten Australian Open champion Sofia Kenin and former world number one Karolina Pliskova in Dubai, and now she is aiming for the biggest scalp of the lot – and Halep knows she will need to be aggressive to upset the upstart's rise.
"It's amazing what [Rybakina's] done already this year," Halep added. "I saw her a little bit during some matches.
"She has a big serve. I have to pay attention on my return and to be like today: confident, aggressive if there is a chance, just fighting. It's the best thing to do now."
World number two Halep had to come from a set down against Rybakina, who put in a wonderful display and came within a break of securing her second title of 2020.
But the 20-year-old ultimately fell short in a final-set tie-breaker as Halep triumphed 3-6 6-3 7-6 (7-5) after two hours and 29 minutes on Saturday.
Halep, a Dubai champion in 2015, saved a break point in just the second game of the match but could not keep Rybakina at bay when the next opportunity came, going long in the sixth to fall behind.
Rybakina saw off two late openings to claim the set, only for Halep to make a brilliant start to the second and soon secure a trio of opportunities, breaking to love when Rybakina failed to pick out the left corner of the court.
Halep was made to work to consolidate the break but then had another two break points in the next game.
However, she passed up both opportunities, allowing Rybakina to roar back and break to love, with Halep signalling for her coach after going wide at the end of the rally.
Halep got the motivation she needed and chances came thick and fast in a mammoth game, which she eventually claimed en route to levelling the match when Rybakina slowed and a fourth break point was taken.
Momentum in the decider similarly swung back and forth, with Rybakina in control when Halep double-faulted before that advantage was immediately cancelled out.
A stunning volley put Rybakina 5-4 up, but Halep rallied to hold serve before breaking in the next game to take a 6-5 lead.
Yet Rybakina was not beaten and, at the second attempt, broke serve to force the tie-break.
Rybakina squandered the chance to take a 6-4 lead in the tie-break on her own serve, though, and Halep duly took advantage, with an overhit return handing the Romanian her second triumph in Dubai.
After battling for a 3-6 6-0 6-4 victory over the 12th seed to reach the last-16 stage, Gauff explained how the decider became a bitterly disputed affair.
She raised a complaint to the umpire in the opening game of that third set over Vondrousova's serving, specifically how the Czech used her racket to control the ball when she got the ball toss wrong. Gauff questioned whether that was permitted.
Vondrousova shot back: "You do the same."
The umpire told both players he had no objections to Vondrousova's play, but the 2019 French Open runner-up seemed affronted by Gauff's remarks and began to scream with delight when taking points off the youngster.
"I was asking when you toss the ball, are you allowed to catch it with your racket," Gauff told a news conference afterwards.
"I thought you had to catch it with your hand or let it bounce first. The umpire said it's allowed if it's not a motion. It wasn't meant to make her upset; it was just asking the question. I left it there, but I could tell she was a bit frustrated by that."
Not to be outshouted, Gauff also turned up the volume when winning points, and she almost hit Vondrousova with a fiercely driven shot as tension mounted.
"My personality, I fight fire with fire," the unseeded Gauff said, quoted on the WTA Tour website. "I lost the last two points of that game and she had wild screams – and I like to scream, so I screamed back."
It was Gauff's seventh successive three-set match, and she turns 17 on Saturday, the day of the final.
Top seed and two-time former champion Elina Svitolina was beaten by Russia's two-time grand slam champion Svetlana Kuznetsova, who at the age of 35 landed an impressive 2-6 6-4 6-1 win.
French Open champion Iga Swiatek saw off Japan's Misaki Doi 6-2 6-4, and Garbine Muguruza scored a 6-4 6-2 win over American Amanda Anisimova.
Muguruza was beaten by Petra Kvitova in the Qatar Open final on Saturday, but Kvitova could not join the last-16 line-up in Dubai, retiring due to injury when trailing 6-2 3-4 against Swiss player Jil Teichmann.
On Monday, Djokovic celebrated a 378th week as the best player in men's tennis, which overtook the all-time record (for men or women) set by Graf.
Like Graf, Djokovic has won 22 grand slam titles, though the 35-year-old remains in the hunt for more glory.
After his Australian Open triumph earlier this season, Djokovic will be hoping a 94th ATP Tour-level title comes his way at this week's Dubai Tennis Championships.
"I still want more achievements," Djokovic said ahead of breaking Graf's record.
"I could not have imagined this, I was dreaming as a kid to be Wimbledon champion, to be number one in the world. I achieved those dreams in 2011.
"After that, I wanted more. Of course, I'm driven by the goals. I'm as dedicated to the sport really as anybody else.
"It's surreal in a way to be that many weeks at world number one, to match Steffi Graf, who is one of the all-time greats of our sport. Just being among these legendary names is flattering. I'm very proud."
Djokovic's campaign in Dubai starts against Tomas Machac on Tuesday.
Muguruza, runner-up at the recent Australian Open, triumphed 6-2 7-6 (8-6) in one hour and 37 minutes on Monday.
Playing her first match since losing to Laura Robson in the second round of the US Open in August 2012, the Belgian was rusty at times as she racked up 10 double faults and gave up 15 break points.
However, Clijsters' fight and impressive groundstrokes in the second set would have given her plenty of hope for the months ahead.
Clijsters' opponent changed when Kiki Bertens withdrew from the event after winning in St Petersburg, but in-form Muguruza represented a similarly daunting first task in her comeback contest.
The 36-year-old was broken in a 10-point opening game and dropped serve again later in the first set.
She forced her first break points as Muguruza served for the opener at 5-2 but could not convert three opportunities as the Spaniard held.
A slow start also impacted four-time major champion Clijsters in the second set, as Muguruza claimed an immediate break and then struck once more in her opponent's next service game to move 3-0 up.
Clijsters showed grit and broke Muguruza for the first time in game four and later superbly claimed a second break to level matters, eventually forcing a tie-break.
She won the first two points of the breaker only for her younger rival to go on a streak of four that included a superb cross-court forehand winner.
At 6-5 in front, Muguruza hit a forehand long on her opening match point but she ultimately sealed victory with her next opportunity thanks to an unreturned serve
Having seen Swiatek brush aside Coco Gauff in straight sets in the first match of the day, Krejcikova would have been confident of doing likewise after taking the opener against Pegula.
Third seed Pegula battled back to take the second set, though, and the American appeared to have momentum on her side, only to bow out in a one-sided decider, losing 6-1 5-7 6-0 for her first defeat to Krejcikova.
The pair's only prior meeting had been a straight-sets win for Pegula at the Australian Open earlier this year.
Pegula's sole other tournament since Melbourne had ended in similar circumstances to this one, with a 6-3 6-0 crushing at the hands of Swiatek in the final of last week's Qatar Open. The Pole is who Krejcikova must play next.
Krejcikova is the first player since Svetlana Kuznetsova in Cincinnati in 2019 to beat two top-three opponents at the same WTA 1000 tournament.
Yet after seeing off number two Aryna Sabalenka in the quarter-finals and number three Pegula in the semis, she faces the world number one in the final.
Swiatek has had a rather more straightforward path, granted a walkover in the last eight and then, on Friday, playing Gauff, who she continues to dominate.
The Pole is now 6-0 across her career against Gauff, winning all of those matches in straight sets.
Gauff at least made Swiatek work a little harder than she has in many recent matches, going down 6-4 6-2 – the first match since Melbourne in which the number one has not won a set either 6-0 or 6-1, piling up the 'bagels' and 'breadsticks'.
Swiatek is 2-1 against Krejcikova for her career, although the Czech won their most recent meeting and their only encounter in a final in Ostrava last year.
By following up victories over Aryna Sabalenka and Jessica Pegula with a ruthless 6-4 6-2 dismantling of Swiatek, Krejcikova became just the fifth woman to beat each of the world's top three players at a single tournament in the last 40 years.
Krejcikova entered Saturday's meeting as the only player to have beaten Swiatek in her eight hard-court finals at tour level, having done so at the Ostrava Open last October.
The Czech looked to be drawing on that experience as she made a flying start, breaking in the opening game through a well-struck backhand.
Though Swiatek responded with a break of her own in the sixth game, a rare double fault from the Pole saw the momentum swing Krejcikova's way.
Another excellent backhand return gave Krejcikova the opening set's decisive break, after which a visibly frustrated Swiatek was handed a time violation by the umpire.
Things did not get much better from there for the three-time grand slam winner, with a series of masterful returns helping Krejcikova seal two dominant breaks before wrapping things up.
Having clinched a highly impressive win within 91 minutes, Krejcikova told Amazon Prime Video: "It means a lot.
"It was a great week for me, I was improving with every single game and today, I think I showed my best.
"I really have to admire Iga for what she is doing. To me, she is a big inspiration and she motivates me every day. It was a great final and I'm definitely happy with the result."
Djokovic had started 2023 by coming out on top in all 15 of his matches and winning the Australian Open, with his overall winning streak standing at 20 games.
But Medvedev ended the world number one's perfect start to the year with a superb display to take a 6-4 6-4 triumph on Friday.
The 27-year-old, who himself made it 13 consecutive wins, broke Djokovic twice on the way to taking the opening set.
Medvedev's high standard of play continued in the second, breaking Djokovic in the first game before holding in all five of his service games to secure a straight-sets victory.
"When you play against Novak you just have to play your best," Medvedev said after the win. "Kind of hope he doesn't play his best on the day because when he plays his best, well he has 22 grand slams, so even if you play your best, it is going to be tough, not sure you win.
"I managed to play a higher level than him today. In the second set I didn't face one break point, but there were so many 30-30 games. But I managed to stay composed and I am happy to be in the final tomorrow."
His win means he will face countryman Rublev in the final after the reigning champion kept his hopes of retaining the title alive with a 6-3 7-6 (11-9) success over Alexander Zverev.
Rublev had never previously won a match or set against Zverev in five previous meetings, but won three of the German's service games in the opener to go a set ahead.
The second seed was out-aced nine to two in the second set but managed to force a tie-break, going on to survive a set point before eventually securing the win on his sixth match point.
Rublev will look to join Roger Federer and Djokovic as only the third repeat champion at the tournament when he takes on Medvedev in Saturday's final.
The compatriots have met six times previously with Medvedev winning four of them, though Rublev has taken victory in their last two match-ups.
Former world number one Medvedev won 6-2 6-2 in an hour and eight minutes, adding to recent victories in Rotterdam and Doha as he extended his winning streak to 14 matches.
It gave him a tour-leading 19th match win of the season, edging ahead of Britain's Cameron Norrie, and means Medvedev will vault above Rublev to reach sixth in the new ATP rankings.
Appearing in his 30th tour-level final, Medvedev picked up his 18th career title and improved his head-to-head advantage to 5-2 against his compatriot.
He broke serve in the first and seventh games to sweep through the opening set, serving out to love to clinch it, and Rublev, who was the defending champion, offered no greater resistance in the second.
After beating Novak Djokovic in the semi-finals, this was supremely clinical from Medvedev, setting him up for tilts at the Masters 1000 events in Indian Wells and Miami over the coming weeks.
"It's amazing," said Medvedev in an on-court interview, "because the start of the year was not perfect."
He lost in round three of the Australian Open to Sebastian Korda, but has put that January jolt firmly behind him.
"In tennis, when you don't win tournaments, you are always doubting, no matter what happens in practice," Medvedev said. "So I was doubting a lot and now it just feels better. I was really happy with these three weeks and I'm looking forward to the next ones.
"Sometimes you feel you're doing all the right shots and you're losing matches, and sometimes you kind of don't even think, just go it, go for some crazy stuff. A lot of shots this tournament were landing which were maybe not supposed to be, and when confidence is going sometimes that helps a lot."
Medvedev's win makes him the third player in the last two years to land three titles in as many weeks, the ATP said, after Casper Ruud in July 2021 and Felix Auger-Aliassime.in October 2022.
Medvedev entered this week knowing victory at the Mexican Open would see him move to the top of the ATP rankings for the first time.
But the Russian was still waiting to play his quarter-final on Thursday when his ascension was confirmed courtesy of Djokovic's last-eight defeat in Dubai.
Djokovic, a seven-time year-end number one, had led the rankings for 86 consecutive weeks, boosting his record total to 361 weeks.
In his first tournament since missing the Australian Open, however, the five-time Dubai champion struggled to match 123rd-ranked Vesely and went down 6-4 7-6 (7-4).
Djokovic might have known what to expect, having lost his only prior meeting with Vesely in Monte Carlo in 2016.
The Serbian looked like getting to grips with his opponent at the start of the second set, applying pressure, but was then broken again and had to respond strongly to reach a tie-break.
Again, Vesely led, and Djokovic's match was summed up by a double-fault immediately after winning back the mini-break, allowing the Czech to prevail.
The victor hailed the end of Djokovic's reign, saying in his on-court interview: "It's great for tennis to have somebody new as world number one again.
"We all know Novak missed the Australian Open, but he's been such a champion, as world number one for 361 weeks.
"Tennis needs new number ones, new generations coming up, so I think it's just great."
As Vesely advances, second seed Andrey Rublev will fancy his chances of a second straight ATP Tour title after his win at the Open 13 Provence.
Rublev stretched his winning streak to seven matches in coming from behind to beat Mackenzie McDonald and make the semi-finals, where he will play Hubert Hurkacz, who defeated Jannik Sinner.
