The Padres won three of the four games in the season-opening series.
The first six San Diego hitters in the fourth reached base against Diamondbacks starter Luke Weaver (0-1). Arizona had taken a 2-1 lead in the top of the third against Padres starter Joey Lucchesi.
Jurickson Profar opened the Padres' fourth by drawing a walk, his fifth walk in four games. Wil Myers followed with a double, sending Profar to third. Profar scored when Greg Garcia singled on a perfectly placed safety squeeze bunt up the first base line.
After Weaver hit Francisco Mejia with a pitch to load the bases, rookie Edward Olivares singled, scoring Myers and putting the Padres ahead 3-2.
Tatis then hit a low rocket past Arizona shortstop Nick Ahmed that rolled all the way to the wall in left-center, scoring Garcia, Mejia and Olivares. Tatis' line drive was clocked at 107 mph off the bat.
In the first inning, Trent Grisham hit his first home run as a Padre.
Ahmed opened the third with a single, his first hit of the season. Lucchesi retired the next two Diamondbacks before Starling Marte doubled home Ahmed to tie the game. Marte then scored on a single by Eduardo Escobar.
Weaver gave up six runs on seven hits and two walks with six strikeouts in 3 1/3 innings.
Lucchesi allowed two runs on five hits and a walk with two strikeouts in 3 2/3 innings. Cal Quantrill (1-0) followed Lucchesi and allowed a hit and a walk with a strikeout in 1 1/3 scoreless innings. Relievers Tim Hill, Luis Perdomo (two innings) and Craig Stammen finished the game by retiring 12 of the 14 Diamondbacks they faced.
--Field Level Media