Giants manager Bruce Bochy announced the news before Friday night's game with the Rays and said right-hander Guillermo Moscoso will take Zito's spot.
"How long this is going to be, I can't tell you, but it was time to change it up so (Zito) will be in long relief," Bochy said. "Sometimes it's just time for a change. You get in a rut."
Zito is 4-8 with a 5.09 ERA in 21 starts this season, allowing 141 hits over 111 1/3 innings. The 2002 AL Cy Young Award winner is 0-7 with a 9.97 ERA on the road.
Bochy said right-hander Ryan Vogelsong is getting close to returning from a fractured right hand.
As for the future of the Giants' rotation, Bochy didn't rule out using a six-man setup.
"We haven't discounted it," Bochy said. "It has been discussed."
The defending World Series champions started Friday last in the NL West.