Pendergraph was injured Thursday night in a preseason game against the Utah Jazz. An MRI on Friday showed he tore his anterior cruciate ligament.
A timetable for his return was not set by the Blazers, but Pendergraph used Twitter to tell fans he was done for the season.
"Tough news today y'all, I'm out for the season with torn ACL," he tweeted.
Pendergraph averaged 2.7 points and 2.5 rebounds in 39 games, including four starts, as a rookie last season.
The 6-foot-9 forward, who played for Arizona State, was the 31st pick in 2009 and acquired by the Blazers in draft-day trade from Sacramento.
The Blazers said the surgery would occur in the next few days.
"Jeff has been playing well and has been a big part of the team, so this is an unfortunate setback," Blazers general manager Rich Cho said. "With his work ethic and determination, we know he'll work hard in his rehabilitation to return to the court."