The 38-year-old striker found the back of the net for the first time in 14 months when he slotted a 93rd-minute penalty past Bristol City goalkeeper Daniel Bentley to seal a 2-1 victory for the Chairboys.
Wycombe fell behind thanks to Tyreeq Bakinson's first-half opener, before Uche Ikpeazu drew Gareth Ainsworth's side level in the 66th minute.
And just when the game looked to be petering out for a draw, Kasey Palmer was penalised for handball, which allowed Akinfenwa to score his first goal of the season.
Wycombe, who have won three of their last five matches, remain bottom of the Championship table, but are now six points from 21st-placed Derby with three games to play.
Akinfenwa's heroics prompted his teammates to rush over to him at full-time to celebrate their crucial victory.
Ainsworth insists he is 'excited' for Wycombe's future - regardless of which division they are in next season.
He said: "I think people can see the upward turn in what's been happening here and, whatever happens, I'm going to be really excited for the future of this football club.
"The future at the moment is Saturday, against Cardiff. If we can get three points there, wow, that could really upset a few teams.
"I'm looking forward to going there and seeing what we can do.
"Tonight, I'll just have a calm down for a minute because it's one of those nights in which chaos has ensued.
"When I saw Bayo pick up the ball for the penalty, Joe Jacobson's usually the penalty-taker.
"He had a knock - I thought he had a nasty injury, but then he walked over and took the corner that ended with David Stockdale's shot gaining the penalty.
"It was just madness and to try and compute it all is impossible. I'm going to have to watch the replays on that one."