Wigan said Glenn Whelan and Graham Barrow will take charge of the first team on an interim basis while the club “will work quickly to identify and appoint” a new head coach.
The club also thanked Lowe for “his efforts and wishes him all the best for the future”.
Lowe previously won promotion from League Two with Bury and Plymouth and finished 13th, 12th and 10th in the Championship with Preston.
Having arrived at the club at the tail end of the 2024-25 season, Lowe guided Wigan to a 15th-placed finish in the table.
After winning against Northampton on the opening day of this season, Wigan’s form soon tailed off as they secured just three victories from 17 matches in all competitions between late August and late November.
Wigan’s next match is at home in the league against Reading on Tuesday (19:45 GMT) before they travel to face Premier League leaders Arsenal in the fourth round of the FA Cup on Sunday, 15 February (16:30).