With his side up 2-0 early in the second half, the Germany international pulled up after slipping while attempting to make a pass.
Neuer had come out to clean up a stray ball and send it back to his team-mates, but seemed to indicate immediately that he would not be able to continue.
Sven Ulreich was summoned from the Bayern bench, while Neuer walked off under his own power, handing the captain's armband to Thomas Muller.
Neuer had recently returned from a calf problem that caused him to miss Bayern's DFB-Pokal quarter-final win against Heidenheim on April 3, being deemed fit enough to feature in his side's 5-0 thumping of title rivals Borussia Dortmund last weekend.
The Bayern No.1 missed almost the entirety of the 2017-18 season with a broken foot, but has played 37 times in all competitions this season.
Ulreich has started just three times in the league, making his first start February 2 in a 3-1 defeat to Bayer Leverkusen — Bayern's only loss in the Bundesliga since January.
He also started the only other game Bayern dropped points since in a 1-1 draw against Freiburg on March 30, though Ulreich was also in goal for a 3-1 win over Schalke in February as well as DFB-Pokal victories over Hertha Berlin and Heidenheim.
Bayern haved return to the Bundesliga summit this weekend after title rivals Dortmund temporarily moved in front following a 2-1 win over Mainz on Saturday.
A brace from Kingsley Coman set the reigning champions on their way against Dusseldorf, with Serge Gnabry also chipping in with a goal and an assist.
Ulreich conceded a late penalty to Dodi Lukebakio, but Leon Goretzka completed the scoring with stoppage time tally to seal the points.
The victory continues a run of fine form in the league for Bayern, as they have taken 43 three points out of a possible 48 over their last 16 games.
It has seen Bayern wipe out a points deficit to Dortmund and now has them a point clear of their title rival, while also possessing a vastly superior goal differential.