Koepka told Lynch his caddie, Ricky Elliott, tested positive for COVID-19.
"I'm going to pull out to protect everybody else," he said. "I think it's the right thing to do. I don't want to risk anyone's life if they have respiratory issues or underlying conditions. The only way this Tour can continue is if guys to do this sort of thing and be proactive about it."
The PGA Tour returned on June 11 with the Charles Schwab Challenge after having suspended the 2020 season because of the coronavirus pandemic.
Nick Watney was the first Tour golfer to test positive.
According to ESPN's Bob Harig, Watney had tested negative for the disease June 16 and proceeded to play in the opening round of the RBC Heritage. However, his fitness tracker indicated an elevated respiratory rate, a sign he might have the coronavirus. He took another test, which came back positive.
The PGA Tour announced Tuesday that Cameron Champ also tested positive and was withdrawing from the Travelers Championship. Shortly thereafter, Graeme McDowell told Lynch he was bowing out as well after his caddy, Ken Comboy, tested positive as well.
Koepka's withdrawal removes one of the top contenders from the event. Caesars Palace listed him at +1200 to win, the joint-second-best odds in the field.
The four-time major champion told Lynch his girlfriend, Jena Sims, and his chef will be tested Wednesday, and the results of their test will determine whether he travels home to Jupiter, Florida, or self-isolates in Hartford, Connecticut.