This is only the second meeting between Wigan and Southampton in the FA Cup, the first ended in a 3-0 win for the Saints in 1986 that Wigan boss Paul Cook featured in.
The last meeting ended in a 2-2 draw between the two sides in 2013 a Premier League game.
Wigan are aiming to knock out their fourth Premier League club from the FA Cup this season. So far, they have eliminated Bournemouth, West Ham and Manchester City.