Stefan Kiessling headed narrowly wide from a second-half corner, but a hole in the side netting left the ball nestling in the corner of the goalmouth.
The striker reacted as if he knew he had missed, but several other players were fooled on both sides - more importantly, so was the referee who awarded the goal to put Leverkusen two goals ahead.
The referee left the field to a resounding chorus of jeers and amid protests from the Hoffenheim players. The Bundesliga does not use goal-line technology nor the additional refereeing assistants who stand on the goal line in European club competitions.
A Hoffenheim official said they would launch a protest while media commentators suggested a replay could be ordered.
Kiessling apologised on Facebook after the game, saying: "I can understand the reactions of many of you one hundred percent and am myself quite upset. According to the replays on TV I see it so clearly: it was not a regular goal.
"In the game I did not exactly see in my header and the turning of the head, whether the ball went into the goal correctly or not. Somehow the ball was in the goal. Exactly what I told the referee.
"I'm sorry for all sports fans and the course of the game. To win like so of course is not good. Fairness is important for the sport in our club and for me personally.”
However Leverkusen sporting director Rudi Voeller had less sympathy for Hoffenheim's plight, saying: "Hoffenheim have spent such a lot of money on a nice stadium. Maybe next time they should buy some proper nets."
He added in an interview with Sky Sports Deutschland: "I couldn't see from the stands but it was clear afterwards that the ball definitely did not go in. "It's unpleasant but there's nothing we can do about it."