The emphatic triumph saw Xabi Alonso's side extend their unbeaten league run to nine matches, moving them up to fourth but still nine points behind leaders Bayern Munich.
However, Leverkusen found themselves behind inside the opening 10 minutes when Niklas Dorsch was teed up by Marvin Pieringer inside the box.
Heidenheim doubled their advantage soon after through Mathias Honsak, who danced his way beyond three defenders before finishing into the bottom left corner.
But two goals in two minutes from Exequiel Palacios and Schick drew the hosts level, with Leverkusen able to take a hold of the contest after the interval.
Schick notched his second of the game seven minutes after the restart to put Leverkusen ahead when he brilliantly flicked Florian Wirtz's cross beyond Kevin Muller.
The Czech striker completed his hat-trick with a header in the 71st minute, with Granit Xhaka sealing the win with a curled finish into the far left corner.
Data Debrief: Patrik hero
Ahead of kick-off, Leverkusen were dealt a huge injury blow with in-form striker Victor Boniface potentially ruled out until next year, but they needn't have worried.
Schick grasped his opportunity with both hands, putting on an impressive display and ending the game with more shots on target (four) and more touches in the opposition box (13), while also accumulating a team-high expected goals (xG) tally of 1.37 to Leverkusen's 2.05 total.
He has now scored three or more goals in a Bundesliga game on three occasions for Leverkusen, with only Ulf Kirsten (seven) having done so more times for the club.
Vincent Kompany's side, who suffered a 1-0 cup defeat to Bayer Leverkusen on Tuesday, were without the injured Harry Kane, Manuel Neuer and Serge Gnabry for the home contest.
And the Bavarians got off to a good start when an unmarked Dayot Upamecano headed in the opener in the 19th minute.
But Upamecano's defensive error five minutes into the second half allowed Mathias Honsak to latch on to his poor back pass and fire past Daniel Peretz to make it 1-1.
However, Musiala, introduced straight after that goal, took just five minutes to make an impact as the 21-year-old's low drive from the edge of the box restored Bayern's lead.
Another Bayern substitute, Leon Goretzka, then added a third with a deflected shot in the 84th minute before Heidenheim pulled a goal back through a Niclas Doresch tap-in.
Musiala then settled the nerves for the hosts as he ran onto a through ball from his own half before scoring in the stoppage time to make it 4-2 with his eighth league goal of the season.
The result sees Bayern extend their lead at the top to six points over second-placed Eintracht Frankfurt, while Heidenheim remain in 16th place.
Data Debrief: Bayern can't stop scoring
Bayern Munich have now scored in each of their last 20 games in the Bundesliga, scoring an incredible 57 goals during that run.
They are also the only side to have scored in each of the 13 games in the German top-flight this season.
Kompany's side, who are unbeaten after 13 games in the Bundesliga, have now matched their last joint longest unbeaten streak, which ran from May 2023 to November 2023.
Heidenheim, meanwhile, have lost five games on the trot now - their longest losing streak in the league since at least the 2004/2005 season.
Adeyemi first set up Donyell Malen, who drilled his low shot through Kevin Muller to give the hosts the lead in the 12th minute.
The 22-year-old then doubled their advantage six minutes later with his first goal after completing a textbook break five minutes later.
Heidenheim briefly cut the deficit with Marvin Pieringer's powerful header after 39 minutes, but Dortmund restored their two-goal cushion before the break with Adeyemi's low drive wrongfooting the goalkeeper.
The visitors set up a nervy finish after being awarded a 74th-minute penalty for a foul by Niklas Sule on Mikkel Kaufmann, with Maximilian Breunig confidently hitting the back of the net.
But Dortmund earned a spot kick themselves in stoppage time thanks to Omar Traore's handball, and Emre Can coolly slotted in to make it 4-2.
Data Debrief: Home advantage
While it looked like Dortmund may be in for a nervy ending after Heidenheim's late penalty, that was not the case, and it means they extend an impressive home record.
The Black and Yellow are unbeaten in 37 Bundesliga home games on a Friday since a 1-0 loss to Schalke in January 2004, which is a league record, level with Werder Bremen between 1984 and 1991).
Dortmund are unbeaten so far this campaign, but Heidenheim's six-match winning run in all competitions is now at an end.
Chelsea are one of six sides, along with Heidenheim, with a perfect record in the competition so far, though the Blues lead the way in the 36-team league table having scored 16 goals in three games.
The Blues' superior goal difference was helped by their 8-0 thrashing of Noah in their last game, scoring six goals in the first-half, which was the largest lead by an English side at the break of a major European game since Derby County were winning 9-0 against Finn Harps in the 1976-77 UEFA Cup.
Though Chelsea have already swept aside the sides put in front of them in the competition so far, Maresca does not want complacency to undermine his side's performance against the Bundesliga club.
"I enjoy every game in this competition knowing that every club tries to make it their big game," Maresca said.
"The issue for us can be that if we are not ready mentally, and we underestimate a team, they can hurt us. So we need to be ready.
"It’s an important competition, a European competition. Since we started, we have tried to share minutes with all the players in the squad.
"In some of the [Conference League] games, we have also used some young players. So we’ll see. In this moment, it’s like this, and hopefully, we can continue in this way."
With the hectic December fixture list to begin on Sunday with Aston Villa's visit to Stamford Bridge, a number of players have not travelled with the squad.
Yet Maresca provided a positive update on Malo Gusto and Pedro Neto, both of whom were absent for their 2-1 victory over Leicester City on Saturday.
"Both have trained with us," he said. "We don’t take any risks for tomorrow’s game, but I think both should be available for Sunday’s game [against Aston Villa]."
BVB moved onto seven points from their first three league games under Sahin with their victory at Signal Iduna Park, as Karim Adeyemi scored twice in between strikes from Donyell Malen and Emre Can.
Since losing 1-0 to Schalke in 2004, Dortmund have not lost any of their last 37 Bundesliga home matches played on a Friday, tying the Bundesliga record.
Only Werder Bremen had previously remained unbeaten at home on Fridays through 37 Bundesliga matches in a row, doing so from 1984 to 1991.
"It was a deserved win and a very good start for us but then we shut the door and I told my players that Heidenheim will not give up. So we had to keep stepping on the gas," Sahin said in his post-match press conference.
"We had a few chances and we could have finished it off earlier but we dealt well with the pressure."
Dortmund, who had new signing Serhou Guirassy in the lineup for the first time following his recovery from injury, quickly took a two-goal lead in the first 17 minutes, Adeyemi teeing up Malen for the opener before getting his first of the encounter shortly after.
"We measure our players also on assists and goals but we can only defend well if the players press. Karim took the momentum from his Germany Under-21 performances with him," Sahin said.
"The first half was our best performance so far but we want to develop further."
Champions Bayer Leverkusen travel to Hoffenheim on Saturday while Bayern Munich, on six points, will look to make it three wins from three games when they take on newly-promoted Holstein Kiel.
Two second-half strikes from Christopher Nkunku and Mykhailo Mudryk kept the Blues top of the pile after four games, taking their total to 18 goals in this year's competition.
The visitors thought they had been awarded a penalty when Mudryk was tripped inside the box, and despite being told to go to the monitor to review the decision, referee Serdar Gozubuyuk stuck with his original call.
However, the Blues found themselves in front six minutes after the break when Jadon Sancho's cross was gathered by Nkunku, who finished with aplomb from inside the area.
Heidenheim continued to ramp up the pressure late on and thought they had levelled through substitute Maximilian Breunig's diving header, but the offside flag was raised on the far side.
The victory was sealed in the 86th minute after fine build-up play between Sancho and Kiernan Dewsbury-Hall saw the ball pulled back for Mudryk, who rifled into the top corner.
Cesare Casadei's sending off in second-half stoppage time took the gloss off an otherwise impressive display, with the Blues' focus now turning to Aston Villa this weekend.
Data Debrief: Blues march on
Following Chelsea's 8-0 thrashing of Armenian minnows Noah in their last game, many placed the Blues as favourites to win this year's competition, but they were made to work for their triumph in Germany.
While the Blues accumulated an expected goals (xG) total of 2.9 to Heidenheim's 1.97, the hosts registered more shots on target (11), but were foiled by the brilliance of Filip Jorgensen, who made 11 saves during the encounter.
Nkunku also continued his scoring streak in the competition, netting his fifth Europa Conference League goal, while also producing more shots on target (three) than any of his team-mates.
In a dramatic second leg of the relegation play-off – with the first encounter having finished goalless – Heidenheim restored parity with a 97th-minute penalty.
However, it was not enough for the home side, with Ludwig Augustinsson's goal three minutes earlier ensuring Bremen stayed up.
The visitors had taken the lead thanks to Norman Theuerkauf's early own goal, but Tim Kleindienst's strike five minutes from time set up a thrilling finale as four-time German champions Bremen – who hold the record for the number of seasons in the Bundesliga – stayed up by the skin of their teeth.
Boniface, who has scored eight goals in 15 appearances in all competitions this season, was replaced late on in the Super Eagles' 2-1 defeat to Rwanda on Monday.
It is another blow for Leverkusen, who have managed 17 points from 10 games so far this season, the worst start to a league campaign in 12 years by a defending champion.
Only Omar Marmoush and Harry Kane (both 11) have scored more goals in the league than Boniface this term (six).
Alonso revealed that the 23-year-old will miss Saturday's Bundesliga encounter against Heidenheim and their Champions League tie against RB Salzburg next week.
"We will have to see how long he will be out. It is a shame," Alonso told a press conference.
"He has a thigh injury. For tomorrow, for Salzburg and maybe a bit longer. We will have to wait and see.
"It is too early to say but we hope he can still play this year. We have to see with the recovery and improvement but it is not a matter of six or eight weeks."
Leverkusen have dropped points in six Bundesliga games already this season (D5, L1), as often as they did during the entirety of their 2023-24 title-winning campaign (D6).
They come into this weekend's fixture against Heidenheim on a three-game winless run in the Bundesliga (D3), the first time they have gone this long without a victory since between April and May 2023 (five games).
Leverkusen sit fourth in the Bundesliga, already nine points behind leaders Bayern Munich as the busy festive schedule kickstarts on Saturday.
Alonso's side have eight games in just under a month, including a DFB-Pokal round of 16 clash with Bayern at the start of December.
"Eight games in four weeks. It is nothing new for us," Alonso said. "An intense phase is coming up for us and it starts tomorrow.
"We have clear goals for the Bundesliga, the Champions League and the German Cup."
The current Bundesliga champions went two goals down inside the opening 21 minutes at the BayArena, before battling back to hammer their visitors.
The teams went in level at half-time, while Patrik Schick completed a hat-trick in the second half to secure their second victory in seven league games.
"The first 20 minutes were hard, hard on the pitch and hard mentally," Alonso told a press conference.
"They bullied us in midfield. We could not find any good situations.
"We then managed to find better solutions after the break, and we were more stable. That was the key to the better second half."
Leverkusen are fourth in the Bundesliga, nine points behind league leaders Bayern Munich. They improved significantly after Heidenheim forward Marvin Pieringer was taken off injured in the 28th minute, having suffered due to his pace prior to that.
"We had a bit of a doubt at the start, it was too hectic, we were too nervous," he added.
"We could relax a bit during the break, and then we saw a much better second half, with more control and more stability. Mentally, we were much better."
Aside from their poor start, Alonso singled out Schick in particular for praise after the game, with his perfect hat-trick having helped win the match for the hosts.
Schick has now scored 3+ goals in a Bundesliga game on three occasions for Leverkusen - only Ulf Kirsten (seven) has done so more times for the club.
"It was a perfect hat-trick. It is so important for a striker to get into this rhythm, to have that feeling and with us having a lot of matches during this time," said Alonso.
Sancho played a starring role in both of the Blues' goals on Thursday, with his driving run helping set up Christopher Nkunku for the opener before teeing up Mudryk to seal a fourth win in the competition.
Neither player has been a regular for the Blues in the Premier League, with Maresca mixing up his options between Premier League duties and domestic and European competition ventures.
Sancho has managed just 312 minutes of top-flight action this season, while Mudryk has only been used for 146 minutes across his seven Premier League appearances, despite notching six goal involvements in the Europa Conference League (three goals, three assists) so far.
But as the English football calendar reaches a busy festive schedule, Chelsea boss Maresca said both players will get their fair share of action.
He told a news conference: "I said since we started, Jadon is very important for us. He has to be fit, mentally and physically and he is going to help us a lot.
"Unfortunately, we did not use him in the last few games but he is showing tonight how important he is. We need that quality in the last third against a low block. He is going to help us a lot.
"He's (Mudryk) one of the players I just mentioned. It's difficult to find players tonight that didn't play well. We need all of them taking the chances when they get the chances.
"They all want to play more; they all deserve to play and are working fantastic. We are going to share minutes in the next games because we have so many games and it's the normal thing to do."
Chelsea lead the league phase of the competition and are on the brink of the last 16. Maresca praised the mentality his side showed to stay perfect in the competition.
"It was a very good challenge for all the aspects, they were high pressing, intense, but no matter what they do, it's important we are ready," he added.
"It's important to continue with that mentality."
It was England winger Sancho who assisted Mudryk for the Blues' second in Thursday's Conference League fixture after Christopher Nkunku scored a second-half opener at the Voith-Arena.
Neither player has been a regular for the Blues in the Premier League, with Maresca mixing up his options between Premier League duties and domestic and European competition ventures.
But as the English calendar reaches a busy festive schedule, Chelsea boss Maresca said both players will get their fair share of action.
He told a news conference: "I said since we start, Jadon is very important for us. He has to be fit, mentally and physically and he is going to help us a lot.
"Unfortunately we did not use him in the last few games but he is showing tonight how important he is. We need that quality in the last third against a low block. He is going to help us a lot.
"He's (Mudryk) one of the players I just mentioned. It's difficult to find players tonight that didn't play well. We need all of them taking the chances when they get the chances.
"They all want to play more; they all deserve to play and are working fantastic. We are going to share minutes in the next games because we have so many games and it's the normal thing to do."
Chelsea lead the league phase of the competition and are on the brink of the last 16. Maresca praised the mentality his side showed to stay perfect in the competition.
"It was a very good challenge for all the aspects, they were high pressing, intense, but no matter what they do, it's important we are ready," he added.
"It's important to continue with that mentality."
Bundesliga leaders Bayern, who lost to Bayer Leverkusen in the DFB-Pokal in midweek, were already without top scorer Harry Kane.
Now two of his team-mates have joined him on the treatment table.
Neuer, who was sent off against Leverkusen, has an issue with his ribs, while Vincent Kompany did not specify Gnabry's injury.
"Manuel Neuer has discomfort with his ribs. It also looks like Serge Gnabry won't be involved either. Aleksandar Pavlovic is available," Kompany told reporters.
"Pavlo is available. There's no limit on how long he can play. He's not played for a while, but he's available."
Kompany did, though, provide a positive update on Kane.
"Things are looking good. I don't want to give a timeline and put our medical team under pressure. It could well be that he plays again this year. But everything needs to go perfectly," Kompany said of Kane.
Bayern are firmly in control in the Bundesliga and are unbeaten after 12 games with 30 points, four more than second-placed Eintracht Frankfurt.
They will fancy their chances of maintaining that unbeaten streak when they take on relegation-threatened Heidenheim, who have lost their last four league games.
However, Kompany warned against complacency.
"They're playing in Europe. It's always tough to be competitive in both competitions. What Heidenheim have done over the last 20 years is good," Kompany said.
"They're a very solid club. They won't panic now. We don't differentiate in how we prepare. It'll be another important game for us."
Heidenheim won their last Bundesliga game against Bayern 3-2 – they became the first promoted team in the league's history to come from two goals down to beat the Bavarians.
The Germany international climbed off the bench to score twice at the Allianz Arena, where he had not found the net in the German top flight since an 8-1 rout of Mainz in March.
Musiala's 11th Bundesliga appearance of the season was his first as a non-starter.
However, he said the breather was welcome and made him feel rejuvenated upon entering the contest, before taking his goal tally for the campaign to 12 in all competitions.
"Recently, I've played a lot of games in a row," he said. "That's why it was good that I got a break and came back energised.
"I've finally scored here in the [Allianz] Arena again. It feels good to celebrate with the fans."
Good morning #FCBayern Fans!
of the log and unbeaten in the #Bundesliga. pic.twitter.com/Ah7XbvVMFV
— FC Bayern (@FCBayernEN) December 8, 2024
Vincent Kompany's side got back to winning ways following their 1-0 defeat by Bayer Leverkusen in the DFB Pokal on Tuesday, in which Manuel Neuer was sent off early on.
And the Bayern boss was pleased by the response of his players.
"We started this week with a tough schedule, played 70 minutes with 10 players against Leverkusen, so it was always a dangerous game for many reasons," he told reporters during his post-match press conference.
"The first half was very good, possession was fluid. The second half - although we stayed calm when we conceded - the last 15 to 20 minutes, the feeling for Heidenheim is totally justified that they are still in the game.
"Still, we created a lot of chances. It was a tough week. We scored four goals. It was still a very, very good day."
