On December 6, 2019, Cronenworth and Tommy Pham were traded to the San Diego Padres in exchange for Hunter Renfroe, Xavier Edwards, and a player to be named later.
Cronenworth made his MLB debut with the Padres on July 26, 2020, and notched a hit and an RBI against the Arizona Diamondbacks. On August 4, Cronenworth hit his first MLB home run off Dustin May in a game against the Los Angeles Dodgers. On August 22, Cronenworth hit his first career grand slam off of Humberto Castellanos of the Houston Astros. Cronenworth was named NL Rookie of the Month in August 2020 after hitting .356 with 16 extra base hits, 17 RBIs and 20 runs over 31 games. Cronenworth finished the season hitting .285 with 4 home runs and 20 RBIs in 54 games. He tied with Alec Bohm of the Philadelphia Phillies for second place in NL Rookie of the Year voting, behind Devin Williams of the Milwaukee Brewers.
On July 4, 2021, Cronenworth was selected to his first All-Star Game as a reserve. In his first game back from the All-Star Break on July 16, he hit for the cycle at Nationals Park against the Washington Nationals.
