Paul Scharner put Wigan ahead after 14 minutes, but Sheffield United striker Jon Stead put the Blades level with a header after 38 minutes.
Former Sheffield United defender David Unsworth kept Wigan up with a penalty after a hand ball from Phil Jagielka.
Sheffield United Danny Webber had the chance to put the Blades level again but hit a post.
Wigan’s Lee McCulloch was sent off in a dramatic second period.