The image of ex-Latics player Max Power on the side of the Speedy Hire business in Queen Street near the town centre was daubed with the large initials WRL.
The letters, which refer to the name of the town's rugby league side the Wigan Warriors, appeared over the weekend.
The mural was put in place to immortalise midfielder Power, now playing at Sunderland, celebrating Will Grigg's title-winning goal against Doncaster Rovers in May 2018.
The footballer is shown wearing a T-shirt bearing the slogan: "No pyro, no party".
Ironically striker Grigg is now a team-mate of Power again after he signed for the Wearside outfit during the January transfer window.
Power himself has now jokingly responded on social media after being made aware of the incident.
He quipped on Twitter: "Am not that ugly am I?"
The photo the mural is based on was taken by Latics official club lensman Bernard Platt.
While many sports fans in Wigan enjoy seeing both town teams do well a section of Latics and Warriors fans have a sometimes-venomous rivalry and reaction to the defacing on social media included plenty of head shaking with concerns that attempts to improve relations will be damaged.
Only recently Wigan Warriors owner Ian Lenagan took to the local press to suggest the two clubs should work together more closely, even mooting the idea of joint season tickets.
The person who claims to be the graffiti artist behind the mural has also now commented in the row.
He said: "The two sporting clubs of Wigan get the type of vandalism each deserves; one nostalgic, considered and a gift to the town. The other delayed because they struggled to get the lid off the emulsion."
He also suggested on Twitter that another mural may now appear somewhere in the town centre.
He wrote: "We go again, bigger and better and obviously with more class."