Hosmer's go-ahead shot against Kyle Gibson with one out in the fifth inning bounced off the top of the right-field wall and into the seats for a 5-2 lead. Austin Hedges, Fernando Tatis Jr. and Manny Machado were aboard for Hosmer's third career slam and fifth homer this season.
Earlier this week, Tatis, Machado and Wil Myers hit grand slams against the Rangers.
Hosmer said the slam streak feels "incredible."
"We were kind of talking about it before the game, just how amazing three was in three games," he said. "The situation came up and it's not really something I was thinking about during the game, but as soon as I got back to the dugout I was thinking about it. Even sweeter is we came away with the win.''
The Padres' grand slam barrage started with Tatis' drive Monday at Texas, when the 21-year-old star shortstop hit an opposite-field shot on a 3-0 pitch with the Padres leading by seven runs in a game they won 14-4. That angered the Rangers, and even Padres manager Jayce Tingler initially wasn't too happy because Tatis missed a take sign before homering. The next day, Tingler said he was happy with the result.
The Padres' slams in three straight games were the most in the big leagues since 2006 and the most in the NL since the Cleveland Spiders hit a grand slam in three in a row against the Boston Beaneaters in 1895.
The Associated Press contributed to this report.