Koepka has won two of the last three U.S. Open tournaments and finished second to Gary Woodland last year at Pebble Beach.
"Unfortunately, I have decided to withdraw from next week's U.S. Open," Koepka wrote Wednesday on Twitter. "I'm looking forward to getting healthy and competing at 100% again very soon."
Last month, Koepka was trying to become the first player since Walter Hagen in the 1920s to win three consecutive PGA Championships. He fell out of contention with a final-round 74 at Harding Park.
Koepka then missed the cut at the Wyndham Championship the following week and withdrew from the first FedEx Cup playoff event -- the Northern Trust -- to end his 2019-20 season.
Koepka, who began the year as the top-ranked golfer in the world, has dropped to No. 8 in the rankings. The four-time major champion underwent a stem cell procedure on his left knee after last year's Tour Championship but aggravated the injury in October. He didn't play again until January.
The U.S. Open begins Sept. 17 after the event was rescheduled from June due to the coronavirus pandemic.