The win was the Padres' third straight to end the four-game series at Petco Park.

With Jose Pirela on first following a game-opening single, Villanueva drove the first pitch he saw from Marlins starter Wei-Yin Chen 378 feet into the left field stands. Villanueva's 15 home runs are the most ever by a Padres rookie before June 1 and the most by a National League rookie before June 1 since Albert Pujols had 16 in 2001.

The Marlins tied the game in the second on Chen's two-run single off Lyles, giving the left-hander from Taiwan his first career RBIs on his 69th at-bat.

The Padres scored two more in the second before Chen (1-3) was replaced after just 1 2/3 innings. San Diego scored three more in the fifth against former Padre right-hander Odrisamer Despaigne.

Lyles (2-1) allowed two runs on six hits and a walk with seven strikeouts in seven innings. In the ninth, Brad Hand struck out J.T. Realmuto with the bases loaded to get his 17th save overall and his 11th in May.

Chen gave up four runs on four hits and two walks with four strikeouts in 1 2/3 innings. Despaigne allowed three runs (two earned) on four hits and three walks with four strikeouts in 4 1/3 innings.

Hosmer put the Padres ahead to stay with a two-out, two-run single in the second. The Padres had loaded the bases on a single by A.J. Ellis and Chen walks to Lyles and Pirela.

Hosmer walked to open the fifth, moved to second on Villanueva's single and scored on Hunter Renfroe's double into the left field corner. Villanueva and Renfroe scored on infield grounders.

Derek Dietrich homered off Kirby Yates for his third hit of the game opening the eighth for the Marlins' final run.

Hosmer added a RBI single in the bottom of the eighth. Pirela, Villanueva and Renfroe all had two hits for the Padres, who finished May with a 15-13 record after a 10-20 start to the season.

The Marlins have lost five of their past six.

--Field Level Media