The four-year veteran out of the University of Texas suffered a spleen injury on Sept. 24 against Carolina.
The designation means Simms, who led the Buccaneers to the NFC South title in 2005, will not play again this season.
He completed 58 of 106 passes for 585 yards, one touchdown and seven interceptions.
In the 2005 campaign, Tampa Bay finished with an 11-5 record after Simms replaced an injured Brian Griese in Week 5.
"I knew there was at least some possibility I could miss the season," Simms told the Tampa Tribune. "It's not the most surprising thing in the world."
Simms' roster spot will be filled by Luke McCown, who was activated from the reserve/physically unable to perform list.
McCown was a fourth-round pick by Cleveland in the 2004 NFL Draft.