The Scot's decisive goal rounded off an unforgettable week for the midfielder who days earlier had become a father for the second time.
McCulloch's goal, scored early in the second half, earned Wigan a remarkable eighth away victory in the Premiership, a total only bettered by Manchester United and Chelsea.
While Wigan had plenty to cheer it was a disappointing afternoon for City whose run of seven successive home victories in league and cup came to an abrupt end.
And it was clearly a case of Stuart Pearce sacrificing Premiership points in pursuit of glory in the FA Cup. After insisting he would field his strongest side against Wigan, the City manager made eight changes to the side that had beaten Aston Villa in their fifth round replay on Tuesday.
And faced with a quarter-final against West Ham on Monday, Pearce clearly wanted to rest key players who had faced the daunting prospect of playing three games in six days.
City almost scored one of the season's most bizarre goals which would have been the highlight of a disappointing opening half.
Wigan keeper John Filan threw the ball out but his clearance struck the back of Sylvain Distin's head as the defender was running away from goal.
The ball looped back over the head of the keeper and struck the crossbar only for referee Martin Atkinson to mysteriously penalise City and award a free-kick to Wigan when there was clearly no infringement.
It was the nearest City came to a goal in a half shaded by the visitors who the previous weekend had also won away at Sunderland.
Wigan came close to taking the lead in the 13th minute when Henri Camara shot narrowly over. City keeper David James also came to his side's rescue making a super save to deny Gary Teale.
Wigan left-back Leighton Baines headed off the line early in the second half after Filan had failed to gather Stephen Ireland's inswinging corner.
But it was Paul Jewell's side that finally broke the deadlock in the 55th minute when McCulloch headed home from six yards out after he had been left completely unmarked.
City's troubles increased when substitute Georgios Samaras, who had replaced the injured Antoine Sibierski, limped off himself after an hour with an ankle injury.
And City also suffered another blow when midfield player Claudio Reyna came off midway through the second half with a shoulder injury.
City had a great chance to equalise seconds from the end of normal time when Trevor Sinclair burst clear on the right but saw his angled drive well saved by Filan, an incident which just about summed up their frustrating afternoon.
Wigan ought to have won by a wider margin as, deep into stoppage time, Jason Roberts burst through on goal only for James to deny him with a splendid save as he looked set to score.
Luckily the miss did not matter as Wigan kept up their impressive run and their challenge for a top-six spot and a place in Europe.