Williams, who signed a five-year, $40 million contract extension prior to the season, has been bothered by a hamstring injury and had missed one game.
Buccaneers coach Greg Schiano said Monday that Williams will undergo surgery on the hamstring.
"Mike had a hamstring injury that he tried to play through," Schiano said. "He just wasn't effective doing it."
In six games this season, Williams had 22 catches for 216 yards with two touchdowns. He had three catches for 20 yards last Thursday against the Carolina Panthers which will end up being his final game of the 2013 season.
A fourth-round draft selection in 2010, Williams has 2,947 receiving yards and 25 touchdown catches in 54 games with Tampa Bay.
The 26-year-old Williams had a career-high 996 yards and nine touchdowns last season.