The result continues a remarkable late-season surge from last year's Champions League finalists, who have now won six of their last seven league matches. Dortmund climb to fifth place on 54 points - just one behind fourth-placed Freiburg - with one match remaining. The top four teams earn automatic qualification for next season's Champions League.
Despite their current form, Edin Terzi's side faced early adversity as Jeremie Frimpong put Bayer Leverkusen ahead in the 31st minute, firing home in what was an emotional final home match for outgoing coach Xabi Alonso.
Alonso, who guided Leverkusen to an unbeaten domestic double and a Europa League final this season, confirmed on Friday that he will step down at the end of the campaign after an impactful three-year spell at the club.
"We experienced a lot of special moments here," Alonso told reporters post-match. "It's a mix of emotions today. What we lived in Leverkusen has been very special - this result won't change that."
While the hosts dominated much of the first half, they were repeatedly denied by Dortmund keeper Gregor Kobel, who made a series of crucial saves to keep his side in the match.
That resilience paid off just two minutes after Frimpong's opener, when Julian Brandt finished off a low cross from Karim Adeyemi to equalize against the run of play.
Dortmund flipped the momentum entirely by halftime. A Leverkusen turnover in midfield allowed Julian Ryerson to finish off a swift transition with a low shot to put the visitors ahead 2–1 in the 43rd minute.
The second half saw Dortmund tighten their grip. Another Leverkusen error in the 73rd minute led to Marcel Sabitzer setting up Adeyemi, who raced in behind and finished confidently to extend the lead.
Just four minutes later, substitute Serhou Guirassy - on loan from Stuttgart - added a fourth with a sharp finish, marking his 20th league goal of the campaign. Jonas Hofmann's late stoppage-time strike for Leverkusen was no more than consolation.
Dortmund will now host already-relegated Holstein Kiel on the final day of the season, knowing that a win could be enough to snatch a Champions League spot - depending on Freiburg's result.
Meanwhile, Bayern Munich - who secured the title last week - celebrated with a 2–0 win over Borussia Monchengladbach on Saturday.
Ole Werner said experience made the difference after RB Leipzig were beaten 3-1 by Union Berlin in Friday's Bundesliga clash at the Stadion An der Alten Forsterei, with all four goals coming in a dramatic second half.
Bayern Munich have stepped up efforts to secure Serge Gnabry's future, with fresh negotiations pointing towards a two-year contract extension that would keep the winger at the Allianz Arena until 2028.
Sebastian Hoeness said his VfB Stuttgart side "did exactly what they came to do" after a commanding 4-1 win over Maccabi Tel Aviv kept their Europa League push firmly on track.
Kylian Mbappe's race to be fit has taken another hit, with the French forward facing a serious battle to return for Real Madrid after remaining unused in their 2-1 defeat to Manchester City at the Bernabeu.
