After a competitive start, the hosts were dealt a huge blow when Charlie Hughes was shown red on 21 minutes.
The 19-year-old was adjudged to have fouled Barnsley frontman Devante Cole, who was bearing down on goal.
And it did not take long for the visitors to take advantage, with Cole latching onto Barry Cotter’s cross from the right to tuck home on 26 minutes.
Wigan had strong shouts for a penalty four minutes after the restart, when Stephen Humphrys was brought down in the area.
But Barnsley should have doubled their lead 20 minutes from time, when new signing John McAtee missed an open goal after a mistake from keeper Sam Tickle before striking the post soon after.
It took a huge save from Liam Roberts to deny Callum Lang an equaliser 11 minutes from the end but McAtee made the result safe when tucking home in added time.