Dr. Ken Akizuki will perform the procedure.
"It's obviously disappointing for Brandon and for all of us," manager Gabe Kapler said Friday. "We've been trending in this direction and Brandon has fought it so hard and wanted to be out there for his teammates and for all of us, and we just weren't able to get over the hump."
Belt had surgery on the same knee in 2015 and 2018. The 34-year-old has faced multiple stints on the injured list with knee inflammation this season, missing 23 games between May 19 and June 14. He last played on Aug. 20.
"He's shown that he can get through major injuries in the past so there's no reason he can't do it again," Kapler said. "When he's right, he's one of the better first basemen in the game."
After hitting a career-high 29 home runs last season, Belt was limited to eight this year, batting .213 in 78 games. He will be a free agent at the end of the season.