The designated hitter, who is in his 19th major league season, is batting .245 with five home runs and 23 RBIs in 49 games.
In other moves, the Padres placed right-handed starter Michael Wacha (shoulder inflammation) on the 15-day injured list (retroactive to Sunday) and optioned right-hander Domingo Tapia to Triple-A El Paso.
Left-hander Jose Castillo, right-hander Matt Waldron and infielder Matthew Batten were recalled from El Paso in corresponding moves.
Cruz, 43, signed a one-year contract with the Padres in the offseason.
He has 464 home runs in his career.