"I told him the other day, it just hasn't worked out," Mattingly said. "I know he hits lefties better than righties. The matchups just never work out on his day. It's always been a righty. So the last couple, at least, he's gotten a lefty. I think that gives him a better chance. You know he feels better when he's able to contribute."
• Grand slams mean 40% off pizza
Mathis, valued for his defense, leadership and handling pitchers, came up big with his bat. The grand slam was the third of his career, and first since June 30, 2013, when he delivered a walk-off grand slam at Marlins Park also against San Diego.
Still, off the bat, Mathis wasn't sure the ball was out.
Statcast™ projected the shot at 367 feet from home plate with an exit velocity of 99 mph and a launch angle of 37 degrees.
"Obviously, it feels good," the veteran catcher said. "I've not been good with guys in scoring position. I'm just happy I've been able to drive those guys in."
Melvin Upton Jr. pursued to the wall before running out of room.
"I know I hit it high," Mathis said. "I saw Melvin kind of tracking it. I was glad to see people catching it."
Mathis entered the game batting .170 with one RBI. With one swing, he had his first home run and broke open a five-run lead.
"It was huge," said right-hander Tom Koehler, who gave up two runs in six innings for the win. "Jeff is such a big part of this team. The things he does on the field and off is tremendous. Everybody pulls for him every time he gets up there. To come up huge like that today, everybody felt great about it. I think we carried the momentum from that homer the rest of the day. It was awesome."
Mathis has played sparingly behind J.T. Realmuto.
Not known for his offense, Mathis still has done better against lefties. He's a career .216 hitter against southpaws to .185 when matched with right-handers.
This year, his left/right splits are .250 (2-for-8) and .167 (7-for-42).
Prior to Tuesday, Mathis' last start was on Friday at Arizona.
Justin Bour belted a grand slam in the seventh. But the blast off reliever Tyler Clippard came after Mathis and Miguel Rojas each walked off lefty Patrick Corbin.
"Today, to be able to get a big hit like that for us, it makes you feel like you're part of it," Mattingly said. "Obviously, he's a big part. To do something like that to help your team win just makes you feel a lot better."