Adrian Gonzalez hit a grand slam and Howie Kendrick added a two-run homer while the Dodgers exploded for nine runs in the first two innings off Mayers and held on for a 9-6 win over the Cardinals on a hot, muggy Sunday night.
Mayers lasted 1 1/3 innings and became the first pitcher to allow nine or more runs with fewer than two innings pitched in his debut since at least 1913.
''Sometimes, it can be more difficult when you have a young kid out there you don't know anything about,'' Dodgers manager Dave Roberts said. ''So for us to get on him earlier and the home run early there by Adrian was big. To see that power surge come was a big boost for us. To tack on another three in the next inning was big for us.
''Then we basically held on.''
Scott Kazmir (9-3) pitched five innings to earn the victory. He allowed three runs on six hits.
''Those first two innings were a battle,'' Kazmir said. ''I didn't have a feel for my breaking ball at all. I didn't have a grip. I was about to get some outs. It was tough out there. I was drenched coming out of the bullpen.''
After a rainout earlier in the week forced a doubleheader, the Cardinals decided not to start Carlos Martinez on short rest and called up Mayers, 24, from Triple-A Memphis for a spot start. St. Louis was the last team in the majors to use a pitcher not in their starting five this season.
Mayers threw 62 pitches and gave up nine runs on eight hits, including two home runs, with about 35 family members and friends on hand. His ERA is 60.75.
''I thought I did a pretty good job with the first two batters and then it felt like it snowballed on me,'' Mayers said. ''I felt like that was the probably the hardest part, just slow the game down. I definitely need to do a much better job of that.''
St. Louis manager Mike Matheny said he felt for his starting rookie.
''He was amped up for sure. Every kid that's picked up a baseball, that's their dream to be in that kind of situation and I thought he had pretty good composure overall,'' Mayers said. ''I thought he was in the zone a good bit but he was so amped up maybe he was overthrowing his off-speed pitches a little where he couldn't put guys away.''
Kenley Jansen got his 29th save in 34 opportunities with a spotless ninth.
The Dodgers scored six runs in a 45-pitch first inning.
Mayers loaded the bases on two singles and a walk. Gonzalez crushed a fastball 427 feet to center for his fifth career grand slam and first since Aug. 26, 2010. After a double by Kendrick, Mayers struck out Yasmani Grandal and got a nice ovation from the crowd. With two outs, Joc Pederson walked and stole second. Kazmir singled up the middle for the final two runs and his first RBIs of the year.
Matt Holliday doubled home a run in the first. It was the first run scored in the first inning by St. Louis since July 3.
After Los Angeles chased Mayers in the second with three more runs, Tommy Pham cut the Dodgers' advantage to 9-3 with a two-run homer in the bottom of the inning.
Four St. Louis relievers combined for 7 2/3 scoreless innings.
In the seventh, Los Angeles failed to score despite four walks.
Dodgers reliever Adam Liberatore allowed three runs in the seventh inning. It was the first runs he's allowed since May 20 - a span that covers 29 games. He had pitched scoreless relief in 41 of his previous 42 games this year.
HOT HOT HOT
The temperature at the start of the game was 96 degrees.
Dodgers: Los Angeles called up RHP Ross Stripling from Triple-A Oklahoma City and optioned LHP Grant Dayton, who threw two scoreless innings in his debut on Friday night. The Dodgers needed a fresh arm after using 17 pitchers in the previous two games.
Cardinals: To make room on the team's 25-man roster for Mayers, St. Louis optioned RHP Miguel Socolovich to Memphis following Saturday's game. Socolovich made two relief appearances while in St. Louis.
Dodgers: RF Yasiel Puig (right hamstring) did not start for the third straight game.
Cardinals: INF Matt Carpenter is expected to begin a minor league rehab assignment this week. Carpenter, sidelined since July 6 with a strained right oblique, took swings in the outdoor batting cage and ran the bases Sunday.
Dodgers: On Tuesday, Bud Norris (5-9, 4.56) will square off against Tampa Bay's Chris Archer (5-13, 4.60). Norris' last start was July 20, but he pitched 1 1/3 innings in relief during Friday's 16-inning game against St. Louis and took the loss.
Cardinals: Martinez (9-6, 2.83) faces the New York Mets' Noah Syndergaard (9-4, 2.43). Martinez logged seven innings in a 4-2 win over San Diego in his last start despite suffering a bloody nose.