Browns head coach Kevin Stefanski confirmed to reporters on Monday that Landry has a sprained MCL.
The 28-year-old rarely misses any action because of injury.
He appeared in all 96 possible regular-season games during his first six seasons in the NFL, only missing his first game in 2020. He later revealed he suffered a broken rib but had stayed on the field.
The receiver remains a consistent weapon as well, totaling at least 70 catches for 750 yards in each NFL season. The production took a dip in 2020, featuring a career-low 72 catches for 840 receiving yards, but the numbers were still enough to lead the team.
Landry is still a go-to option for Cleveland when healthy, totaling 71 receiving yards on five catches in Week 1.
With Landry now out and Odell Beckham Jr. still inactive, the Browns turn to Donovan Peoples-Jones, Rashard Higgins and Anthony Schwartz at receiver.