Willis’ retirement will clear $7.4245 million from the team's 2015 salary cap. He still has two years remaining on a five-year, $50 million contract he signed in 2010.
Willis played in six games for San Francisco in 2014, recording 49 tackles, three passes defensed and one interception before being placed on injured reserve in November with a toe injury.
Willis, 30, was the team’s first-round selection in the 2007 NFL draft and was named AP Defensive Rookie of the Year.
He made the Pro Bowl in each of his first seven seasons in the NFL and was a five-time first-team AP All-Pro selection.
Willis said in November that he was looking forward to getting back to 100 percent this season.
"To most, it probably looked like, ‘Man, Willis is losing a step,’" Willis said, according to CSNBayArea. “But I promise you, physically and mentally, I’m just as good now as I was early on. But unfortunately the one thing I needed most to make me who I am are my feet. My left side, without a big toe, it’s like trying to grab without a thumb. You just can’t do it."
Willis started 112 games in his career and recorded 20.5 sacks with 16 forced fumbles, eight interceptions and five fumble recoveries.