Although the 37-year-old Wawrinka is no longer at his best – ranked 322nd in the world – he still put up a strong fight against his 23-year-old opponent, creating eight break point opportunities in the match while facing nine.
Ruusuvuori will play eighth seed Hubert Hurkacz in the second round in a tough matchup, while Slovakia's Alex Molcan will play fourth seed Casper Ruud after defeating American Mackenzie McDonald 7-6 (7-1) 6-4.
Molcan's advantage was in his serve, winning 74 per cent (49-of-66) of his service points compared to 59 per cent (49-of-83) for McDonald.
In a clash between a pair of top-30 talents, Russia's Karen Khachanov got the better of Argentina's Francisco Cerundolo 7-6 (7-4) 5-7 6-3. He will play the winner between 13th seed Marin Cilic and Croatia's Borna Coric next.
Recent runner-up of the Atlanta Open Jenson Brooskby had no issues with Kazakhstan's Alexander Bublik, winning 6-2 6-3, and he will likely play Roberto Bautista-Agut in the second round as the Spaniard leads 7-6 (7-5) 2-1 with a break in the second set when a rain delay ended the day's play.
One of Canada's top hopes, Denis Shapovalov, will have his back up against the wall when his match resumes against Alex de Minaur, losing the first set 7-5, with the rain arriving in the middle of the second-set tiebreaker.
Jack Draper will head back onto the court with a set advantage against Hugo Gaston after winning the opener 6-2, although he will have to save a break point first up.
Thiem finally ended his wait for a first major title in New York earlier this month, beating Alexander Zverev in a five-set epic after losing his prior three finals.
Two of those came in the most recent two French Open finals against Rafael Nadal, although there will be no repeat this year.
Thiem is in the bottom half of the draw along with Nadal, who starts against Egor Gerasimov, and has a tricky schedule right from the outset.
The Austrian has grand slam winner Marin Cilic in the first round, and Andy Murray and Stan Wawrinka – two other former major champions – are potential fourth-round opponents as they begin against one another in an intriguing clash.
Nadal could have to tackle John Isner in the last 16, while Zverev is also in the bottom half of the draw.
World number one Novak Djokovic has Mikael Ymer up first and could meet Pablo Carreno Busta in the quarter-finals, having been defaulted from the US Open when facing the Spaniard – his only defeat of the year.
Daniil Medvedev and Stefanos Tsitsipas are in the top half, too.
Meanwhile, Williams, still bidding for a record-equalling 24th major title, is set to meet Victoria Azarenka in round four.
Azarenka came from a set down to beat Williams in the semi-finals at Flushing Meadows before she was defeated in the championship match by Naomi Osaka, who is absent in France.
Defending champion Ash Barty and 2019 US Open winner Bianca Andreescu are also missing, while world number 10 Belinda Bencic withdrew shortly before the draw.
But Williams still faces a difficult task just to reach the final.
A potential victory over Azarenka in the last 16 could see the 38-year-old paired with third seed Elina Svitolina in the quarters, while top seed, world number two and 2018 champion Simona Halep is also in the same half.
Williams starts against Kristie Ahn, who she defeated in her US Open opener.
Kiki Bertens is in the same quarter as Halep, which sees arguably the pick of the first-round matches as Coco Gauff takes on Johanna Konta, last year's semi-finalist.
Marketa Vondrousova, beaten by Barty in the 2019 final, is a potential fourth-round opponent for Halep.
Karolina Pliskova and Petra Kvitova are in the same section as former champion Jelena Ostapenko and Germany's Angelique Kerber, who could complete a career Grand Slam.
Garbine Muguruza, another previous winner, is in Sofia Kenin's quarter with Aryna Sabalenka.
Thiem, the former world number three who hasn't played since 2021, started slowly and fell 5-0 behind in the first set against the world number 228.
He improved in the second set but was not able to recover from dropping serve in the first game.
"Obviously, the result today is the bitter part," Thiem posted on his Instagram. "I would have wanted to win, and I have to accept the defeat in a humble manner.
"This is only the beginning of a long way to the top of my game."
Three-time grand slam champion Wawrinka, whose most recent major success came at the 2016 US Open, was competing in just his second ATP Tour match in 14 months after recovering from a foot injury but battled past American Opelka 3-6 7-5 6-2 in Rome.
Opelka seemed to hold the initiative after dominating the first set and boasting a 4-2 advantage in the second, but the 37-year-old Swiss recovered well to fight back against the world number 17.
Wawrinka managed to release his heavy-hitting forehand and close the court by nearer to the net, with Opelka providing no response as the former world number three triumphed in two hours and five minutes.
Laslo Djere or Borna Coric will be the second-round opponent for Wawrinka, who registered his first tour-level win since February 2021.
Before defeating Opelka, Wawrinka had not won a match since he defeated Pedro Sousa at the Australian Open last season.
His only other ATP Tour match since then ended in defeat to Alexander Bublik in Monte Carlo last month.
Alcaraz was in control, winning the first set in 36 minutes before racing to a 2-0 lead inside 10 minutes before the Briton withdrew. Draper had battled the injury in the latter stages of Monday's win over Andy Murray.
Despite that, the Spaniard looked in good touch, setting up a quarter-final meeting with eighth seed Felix Auger-Aliassime, who has a 3-0 head-to-head record against him.
"I felt the ball really well. I'm really happy with that part," Alcaraz said. "I would say I returned well, I hit great shots. I finished the match with confidence in my shots, to come into the next round with more confidence."
Auger-Aliassime saved six match points in a dramatic triumph over 17th seed Tommy Paul to reach the last eight, winning 3-6 6-3 7-6 (8-6) in two hours and 48 minutes.
The Canadian trailed 0-40 on serve at 5-6 in the deciding set before winning the next five points. He repeated that feat, down 3-6 in the tie-break, capitalising on his first match point. Auger-Aliassime hit 31 winners for the match, along with 51 unforced errors.
Fifth seed Daniil Medvedev fought back from a set down and a rolled ankle to progress past Alexander Zverev 6-7 (5-7) 7-6 (7-5) 7-5 in three hours and 10 minutes.
Medvedev rolled his ankle in the sixth game of the second set, going down in pain but played on, in his longest-ever three-set match. The victory is the Russian's 17th in a row. Zverev committed 50 unforced errors across the match.
The Russian will take on Alejandro Davidovich Fokina in the last eight, with the Spaniard winning 6-3 6-4 over Chilean qualifier Cristian Garin.
Jannik Sinner cruised past Stanislas Wawrinka 6-1 6-4 in one hour and 39 minutes to move into the last eight where he will face reigning champion Taylor Fritz. The American won 6-4 6-3 over Hungary's Martin Fucsovics in one hour and 41 minutes.
British 10th seed Cameron Norrie will play 14th seed Frances Tiafoe in the other quarter-final, with the former winning 6-2 6-4 over the higher-ranked Andrey Rublev. Tiafoe won 6-4 6-4 over Alejandro Tabilo in 83 minutes for his 150th career win.
In his first match of 2020, top seed Wawrinka saved six of the seven break points he faced and came from 0-3 down in the second set to book a meeting with Aljaz Bedene, who overcame Alexander Bublik 6-3 7-5.
Laslo Djere defeated Lorenzo Sonego 6-1 3-6 6-2 and Mikhail Kukushkin downed Malek Jaziri 6-0 6-3, earning a clash with second seed Andrey Rublev in round two.
Wawrinka's doubles partner Frances Tiafoe – seeded eighth in the singles – lost 6-4 4-6 6-4 to Marton Fucsovics, while Pierre-Hugues Herbert and Cem Ilkel also progressed.
The ATP released a statement on Monday saying an unnamed player is now isolating after testing positive for the virus and a contact-tracing process is underway to notify people who may have come into contact with him.
While they did not confirm Querrey was the player in question, the American no longer features on the draw and his first-round opponent, Denis Shapovalov, is now scheduled to play lucky loser Viktor Troicki.
On court, meanwhile, Stan Wawrinka saved three match points to overcome Dan Evans 3-6 7-6 (7-3) 7-5, wildcard Aslan Karatsev saw off Tennys Sandgren 7-5 3-6 7-5 and Cameron Norrie edged past eighth seed Taylor Fritz 6-4 4-6 6-3.
In Cologne, Oscar Otte beat Jan-Lennard Struff in an all-German clash, while Steve Johnson saw off Filip Krajinovic – the fifth seed – in a deciding set.
At the Forte Village Sardegna Open in Italy, teenager Lorenzo Musetti boosted his burgeoning reputation by beating Pablo Cuevas in straight sets, while Jiri Vesely overcame Kamil Majchrzak.
Three-time grand slam winner Wawrinka, who is the oldest player in the main draw, hit back in the Spanish capital to progress 6-7 (7-3) 6-3 7-6 (7-4).
The 38-year-old won 46 of 54 first-serve points and now has a couple of days to recover before facing fifth seed Rublev, who was handed a bye to the last 32.
Roberto Carballes Baena is also through after defeating David Goffin 6-4 6-4, with Alexander Zverev up next, while Alex Molcan saw off Wu Yibing 6-2 6-4.
There was a shock elsewhere on Wednesday as Diego Schwartzman was downed in straight sets by Hugo Grenier.
On the same day fellow countryman Roger Federer would hang up his racquet at the Laver Cup, Wawrinka was forced to go all the way by his opponent in Metz, eventually winning 6-4 4-6 7-6 (7-5).
The three-time grand slam champion, whose injury struggles and form have seen him tumble to 284 in the world rankings, served up seven aces to Ymer's two, and made no double faults.
Victory moves him into the last four, where he will meet seventh seed Alexander Bublik after the Kazakh saw off Holger Rune in another three-set encounter with a 6-3 5-7 6-4 win.
Defending champion Hubert Hurkacz is also through to the semi-finals after making quick work of home favourite Arthur Rinderknech, winning 6-3 6-2.
The world number 10 will face Lorenzo Sonego next after the Italian also came through his quarter-final in straight sets against Sebastian Korda.
The pair, both three-time grand slam winners, enjoyed contrasting fortunes in their first-round matches against Tallon Griekspoor and Alex de Minaur.
Wawrinka, who has not played since Indian Wells last month, saw off the Dutchman in a 5-7 6-3 6-4 triumph, but Murray was routed by the Australian in a 6-1 6-3 loss.
"It was really important to stay calm with myself," Wawrinka said. "In the first round you need to find your game. I am happy to get through. It was important to fight until the end."
Roberto Bautista Agut saved a match point in the second-set tie-break as he fought back to overcome Filip Krajinovic to prevail 5-7 7-6 (12-10) 6-1.
Dominic Thiem is also through following a 6-1 6-4 win over Richard Gasquet but 11th seed Cameron Norrie is out after suffering a 6-3 6-4 loss to Francisco Cerundolo.
Former world number one Murray pulled off a remarkable win over Russian Roman Safiullin, winning five games in a row from 4-1 behind in the final set.
But that was just a tease for the excitement that followed, as Wawrinka, who like Murray won three grand slam titles in his prime, felled second seed Ruud in straight sets.
The 37-year-old Swiss delighted his home crowd with a 6-4 6-4 victory over this season's French Open and US Open runner-up, serving nine aces as he defied a world ranking of 194th to produce some of his old magic.
Murray has fallen away from the elite ,too, but at 49th in the world he is not far away from rejoining that pack, although defeat looked to be beckoning against Safiullin.
The 35-year-old Scot fist-pumped with relief at recovering the break of serve that Safiullin snatched early in the decider, and Murray hit a service winner on his second match point to seal a 6-7 (5-7) 6-3 6-4 success.
The victory for two-time Wimbledon winner Murray took him to 26 wins this season, the most he has had in a single campaign since pulling off an astounding 78 victories in 2016, the year he won at the All England Club for a second time, landed a second Olympic gold medal and finished top of the rankings.
Murray said of his win: "As the match went on, I started to dictate a few more points and served better."
Quoted on the ATP website, he added: "I changed the way I was returning a little bit, and when I did that, I was able to create a few more opportunities and frustrate him a little bit."
Pablo Carreno Busta scored a 6-2 6-1 win against Argentinian Sebastian Baez, with Alex Molcan, Dominic Stricker and Botic van de Zandschulp also advancing to the last-16 stage.
At the Vienna Open, Murray's fellow British players Cameron Norrie and Dan Evans both went through to the second round, Norrie beating Argentina's Pedro Cachin 3-6 6-2 7-6 (7-1) and Evans fending off Germany's Oscar Otte 6-4 7-6 (7-3).
Canadian left-hander Denis Shapovalov beat Austrian wildcard Jurij Rodionov, but the home crowd had something to celebrate when former US Open champion Dominic Thiem continued his resurgence by eking out a 2-6 7-6 (7-2) 7-6 (8-6) victory against American Tommy Paul, saving two match points.
Wawrinka, the third seed at the ATP 500 event in Acapulco, needed two hours, 45 minutes to edge Frances Tiafoe 6-3 6-7 (4-7) 7-6 (7-1).
The Swiss three-time grand slam champion squandered four match points before battling through.
Wawrinka was the only seed in action on Monday, as two American qualifiers – Tommy Paul and Marcos Giron – progressed.
Adrian Mannarino overcame wildcard Cameron Norrie 2-6 6-3 6-3, Miomir Kecmanovic edged past Alex de Minaur 3-6 6-4 6-3 and Kyle Edmund hammered Feliciano Lopez 6-4 6-1.
At the Chile Open, sixth seed Hugo Dellien got through the first round, while Roberto Carballes Baena and wildcards Thiago Seyboth Wild and Marcelo Tomas Barrios Vera also won.
Wawrinka came through two qualifying matches to take his place in the main draw before defeating Sousa 7-6 (7-1) 6-2 in Metz on Wednesday.
The three-time grand slam champion's victory was only his fourth in a main draw at tour-level this year following a 13-month absence due to a foot injury.
Wawrinka said after setting up a showdown with top seed Medvedev: "It's the first time I won three matches in the same tournament for more than two years, so it's great.
"I'm getting confidence from winning a few matches, so I'm feeling a bit more relaxed, the way I'm moving. I think the level was good from me, and I'm happy with the win."
Dominic Thiem also advanced at the indoor hard-court event, seeing off Richard Gasquet 6-3 7-6 (7-3).
Sebastian Korda was the first man to seal a quarter-final spot, sending third seed Lorenzo Musetti packing with a 6-3 7-6 (8-6) victory in the last match of the day.
Meanwhile, Alexander Bublik, Gregoire Barrere and Benjamin Bonzi were the other first-round winners.
The former world number three made his comeback after more than a year out with a left foot injury that required two surgeries but fell to a 3-6 7-5 6-2 defeat to Alexander Bublik in the first round.
Wawrinka, who entered the tournament as a wildcard having slipped to 236 in the world rankings, came from a break down to take the opening set but fatigue eventually set in and he was eliminated after two hours and seven minutes.
"I think the body's getting much better," said Wawrinka, who lost in straight sets to Elias Ymer at a Challenger tournament in Marbella two weeks ago.
"I'm still far away from where I want to be, but I think I'm [going in] the right direction. I think today was a positive match. It was a tough loss, of course, but I'm happy with the way I was playing today.
"I was playing better, feeling better on the court physically. I spent a lot of mental energy to focus, to stay there as it was tough at the end. But I'm happy with what I have done."
Ninth seed Sinner was taken the distance by Coric before completing a 6-3 2-6 6-3 victory to advance to the second round.
Sinner took a medical timeout in the second set while he dealt with some apparent abdominal pain, but he was able to battle back and take the win.
Diego Schwartzman needed over three hours to come from behind and defeat Karen Khachanov 6-7 (5-7) 6-3 6-3, while his fellow Argentine Federico Delbonis set up a clash with second seed Alexander Zverev by besting Jaume Munar 6-4 3-6 6-4.
Reigning champion Stefanos Tsitsipas faces a meeting with Fabio Fognini in the second round after the Italian overcame Arthur Rinderknech 7-5 4-6 6-3.
There were also wins for Hubert Hurkacz, Pablo Carreno Busta, Marin Cilic, Alex de Minaur, Albert Ramos-Vinolas and Sebastian Korda.
A 17-time grand slam champion, Djokovic is still behind Federer (20) and Nadal (19) on the all-time list for majors won by men, while the Serbian still struggles for support compared to the Swiss and Spaniard.
In an Instagram Live with Stan Wawrinka on Saturday, Djokovic discussed why that was the case, accepting he would often find himself on the wrong side of the support against the duo.
"For sure one thing is that Roger is arguably the greatest player of all-time," he said.
"He's the guy that is liked around the world so I don't expect, to be honest, in most of the cases, as long as he's playing, the crowd to be majority on my side. Some places, maybe, but most of the places are going to support Roger and I'm okay with that because it's Roger.
"It's very similar situation with Rafa so it's hard for me to answer to that question. Why is it like that? Am I contributing to that in a negative way that I'm taking away the crowd support for me? I don't think so.
"I think it's more just the greatness of Roger Federer and Rafael Nadal and not just them as tennis players, but them as people, as very charismatic, nice guys, humble guys, great champions that have made a huge mark in our sport and I am part of their era, so in one way I am lucky and in another way maybe not so much."
Djokovic asked Wawrinka – a three-time grand slam champion – for his opinion on the matter.
The Swiss felt tennis needed something closer to a villain, a role the 32-year-old Djokovic assumed.
"I think it's a bit of for sure what you said that they are amazing champions like you are," Wawrinka said.
"I think in your young age you were a bit different of course like we all are and they took this spot already of the nice player, humble, always fair play and all. In a movie you cannot have three good guys, you need someone who's a bit against, you know what I mean? I'm saying that with a lot of respect.
"When you were all three younger, that's the direction that everybody took a little bit and now it affects a little bit right now."
