After six full seasons in Houston, Caminiti was traded to the San Diego Padres after the 1994 season in a 12-player trade, along with Steve Finley, Andújar Cedeño, Roberto Petagine, Brian Williams, and a player to be named later (PTBNL), in exchange for Derek Bell, Doug Brocail, Ricky Gutiérrez, Pedro Martínez, Phil Plantier, and Craig Shipley. In San Diego he reached career highs at the plate by hitting .302 with 26 home runs and 94 RBI in 1995, which rose to .326/40/130 in 1996. Despite playing most of 1996 with a torn right rotator cuff, his performance earned him the National League Most Valuable Player Award. In 1998, Caminiti led the Padres to the 1998 World Series where they lost to the New York Yankees in four games.
Caminiti won three Gold Glove Awards while playing for the Padres in 1995, 1996, and 1997, and he was unanimously selected as the National League's MVP in 1996. In 1994, 1996, and 1997, he appeared in the All Star Game. Caminiti is the Padres All-Time leader in slugging percentage (.540) and OPS (.924).