Beltran's three-run homer sparked a seven-run third inning Thursday and the Cardinals got seven stingy innings from Wainwright to open their National League division series with a 9-1 rout of the Pirates.
"To be able to get out on a good first step and play well today I think is big for our guys confidence-wise," St. Louis Manager Mike Matheny said. "Gives us an opportunity to just take some momentum, and momentum is big right now when you talk about a five-game series."
The first eight Cardinals reached safely in the third to chase A.J. Burnett, saddling the right-hander with the second-shortest outing of his career and putting Game 1 out of reach early.
A sellout crowd roared and then settled in for an easy victory by the NL Central champions, who are making their third consecutive trip to the postseason.
"Game 164 was rough," Pirates Manager Clint Hurdle said. "One of the things we've been good at is we don't overcook things."
Lance Lynn (15-10) faces Pittsburgh rookie Gerrit Cole (10-7) in Game 2 on Friday.
After a record 20 straight losing seasons, the Pirates are back in the playoffs for the first time since 1992. They entered their first best-of-five division series with plenty of momentum after beating Cincinnati in the wild-card game Tuesday, but Pittsburgh never threatened to rally against Wainwright and finished with only four hits.
Pittsburgh also was sloppy in the field, committing three errors. St. Louis was sharp on defense, with reliever Carlos Martinez turning in the top play by slinging an off-balance throw to first to nip Russell Martin in the eighth.
"What a play!" Matheny mouthed in the dugout.
Wainwright remained unbeaten in the postseason, going to 3-0 with a 2.27 ERA in 14 games, five of them starts.
He allowed a run on three hits in seven innings, striking out nine without a walk. The only damage came on a homer by Pedro Alvarez to start the fifth.
The right-hander tied for the NL lead with 19 wins this year and was 4-0 in his last five starts. He thrives on expectations.
"I'd love to be that guy," Wainwright said. "It's important to have somebody go out there that you can count on for sure."
Wainwright also started the Cardinals' big burst with a leadoff, full-count walk.
Beltran, who has never reached the World Series, reprised his role as one of the game's greatest playoff sluggers. His 443-foot drive to the distant second deck in right field put St. Louis ahead and was the second-longest shot by a left-handed batter at 8-year-old Busch Stadium.
"I almost got caught up in the moment," said Wainwright, who had a perfect view from second base. "I threw my hands up in the air as soon as he hit it, I knew it was gone.
"Then I realized I had to run."
Beltran has 15 home runs, 10 doubles and 28 RBIs in 35 postseason games. He also has scored 40 runs and stolen 11 bases.