The Warriors have won the Challenge Cup a record 18 times, including eight years in a row between 1987 and 1995.
They are 3/1 with Apollo Bet to repeat their success of last season, where they defeated Leeds in a gripping contest at Wembley.
An Apollo Bet spokesman said: “Wigan have a rich heritage in the competition, and as the holders, the Challenge Cup is theirs to lose.
“They are definitely the team to beat in the knockout tournament this season, and they will be expected to win their opening game comfortably.”
Second favourites are Warrington (7/2), who won the competition in 2009 and 2010.
Last season’s finalists Leeds are 5/1, while Catalan, Huddersfield and Hull are all 14/1.
Click here for Challenge Cup betting with Apollo Bet.