Athletic trainers first came out to check on Lyles after Hunter Pence's single in the fourth and again following Matt Duffy's RBI single two batters later. Lyles finished the inning but faced only three batters in the fifth -- the last being Joe Panik, whom he hit -- before exiting with an athletic trainer by his side.
Weiss said the injury was affecting Lyles' follow-through -- the final indication that a pitching change needed to be made.
"He got to the point where we felt like he was spinning off, trying to protect that land foot," Weiss said.
Lyles lasted four-plus innings, giving up seven hits and six runs (five earned). The Giants first got to him in the fourth, banging out four consecutive two-out singles to grab a 3-0 lead.
Before the injury, though, Lyles appeared locked in. He didn't surrender a hit in the first three frames and struck out four of the Giants' first nine hitters.
"Obviously, he's a tough competitor and wanted to stay in the game," Rockies catcher Nick Hundley said. "But I think the choice was made for him."
Dargan Southard is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.