From Georgia, Mike Wilson was taken in the fourth round (103rd overall) of the 1977 NFL Draft. The imposing offensive lineman initially opted to head north, signing with the Toronto Argonauts of the Canadian Football League for the 1977 season, where he immediately earned CFL All-Star honors. He joined the Bengals in 1978, stepping directly onto the field as an NFL-ready starter.

At 6 feet 5 inches and 273 pounds, Wilson possessed the length, quick footwork, and functional power to hold down the perimeter. He stepped right into the starting lineup at left tackle for his first two seasons (1978–1979), protecting the blind side before shifting over to right tackle in 1980.

Wilson became an essential pillar on the offensive front during Cincinnati's 1981 AFC Championship run, starting every game and protecting Ken Anderson during his MVP campaign en route to Super Bowl XVI. Known for his game-in, game-out consistency, Wilson put together four separate seasons in Cincinnati with a double-digit Approximate Value rating, proving to be one of the most dependable tackles in the conference.

His eight-year run with the Bengals came to a close after the 1985 season, after which he spent his final professional campaign with the Seattle Seahawks in 1986 before retiring.  He started all but two of his games for the team.