The blaze broke out Sunday morning in the basement of the three-storey structure on Bannatyne Ave. in the city's downtown Exchange District and eventually burned to the roof.
The building has been undergoing renovations and no one was inside at the time, but it took firefighters several hours to get the flames under control.
People living nearby were told to leave their homes in case the fire spread.
The album cover was for The Guess Who's 1971 release "So Long, Bannatyne," which included such songs as "Rain Dance," "Sour Suite" and "Albert Flasher."
The group — which was riding a wave of international acclaim at that time — came up with the title because guitarist Kurt Winter had been living in an apartment on Bannatyne and moved out that year.
Greg Duncan, a Guess Who fan who witnessed the fire, passes the block daily on his way to work and told CTV Winnipeg it's the same one used for the album art.
"It's kind of an interesting building. It's just something I walked by quite frequently and thought, 'I wonder if it's still there?' So I started looking as I was walking and sure enough, that's it."
There was no immediate word on the cause of the fire or the damage estimate. (CJOB, CTV Winnipeg)