Goals from Joe Ironside and Adam May gave Cambridge a two goal lead and the hosts looked to be on their way to an impressive victory until goals from Will Keane and Callum Lang rescued a point for Wigan late on.
The Latics are in fourth place in the EFL League One table, two points away from the automatic promotion places, while the U's are mid table in 15th.
Story of the match
Wigan thought they had taken a ninth-minute lead as Keane found the back of the net, but the referee's flag waved the goal back for offside.
The Latics appealed for a penalty when Lang beat Conor Masterson and the Cambridge defender took him down, but in the end no penalty was given.
Dimitar Mitov was then called into action as he stopped Max Power's low drive and made a brilliant save to deny Lang from close range.
Against the run of play, the hosts took the lead. A long throw by Jack Iredale was headed into the box by James Brophy and Ironside was there to volley home the opener.
In the 53rd minute, the U's doubled their lead as May met Ironside's knockdown and found the bottom corner with a left-footed strike from the edge of the box.
Mitov then saved low from Lang as the match ticked towards the closing stages, but Wigan responded in the final few minutes with a stunning response.
With just six minutes of the game to play, Keane struck with a shot that went in off the left upright and three minutes later, Lang turned home James McClean's free-kick to complete the comeback in dramatic fashion.
Man of the match: Callum Lang
He was a threat throughout the entirety of the game for Leam Richardson’s side, creating several good chances for his teammates and his equaliser was the very least he deserved for such a positive and impressive performance on the night.