Verrett had an MRI on the knee last week and has decided to have surgery.
"It was never right in my opinion, just watching him in practice," Chargers coach Anthony Lynn said. "But he's such a competitor [that] he kept wanting to go out, save himself and play the first week. But he wasn't able to play to his standard. So we just want him to get healthy."
Verrett, 26, shut it down last season after a Week 4 game against the New Orleans Saints, when an MRI revealed he had a partially torn ACL in his left knee. After having surgery to repair the issue, the TCU product endured a rigorous rehab to work his way back onto the field.
The Chargers took a cautious approach with Verrett this year, holding him out of offseason work on the field and slowly working him back into training camp. Verrett played in just one preseason game, against the Los Angeles Rams.
He played 63 snaps in the team's opener against the Denver Broncos, but experienced soreness in his knee and missed the last two days of practice last week, with Lynn ruling him out for last Sunday's game against the Miami Dolphins.
With Verrett out for the season, he will have missed 39 of a possible 64 games in four seasons with the Chargers. He was a first-round pick in 2014 and played in the Pro Bowl after the 2015 season.
In a corresponding roster move, the Chargers promoted linebacker Nick Dzubnar from the practice squad.
ESPN's Eric D. Williams contributed to this report.