Having already hit a three-run homer and RBI single, Beltran blasted a 2-0 pitch from Pirates starter A.J. Burnett to center with two out in the third. The ball bounced off the top of the outfield wall and was initially ruled a double by second-base umpire Dale Scott.
Cardinals manager Mike Matheny immediately emerged from the dugout and requested the umpiring crew review the play, which it did.
"It looked like it got to a fan, so that's why I came out," Matheny said.
Several minutes later, the umpires returned to the field and signaled for Beltran to finish circling the bases.
This marked the first time that the Cards have had instant replay used in a game this season.
"When I hit it, I knew it was a line drive," Beltran said. "It could have been off the wall or it could have been gone. That's why I stayed at second base. I wasn't sure if the ball left the ballpark. But thank God it left the ballpark."
With the initial decision overturned, Beltran was credited with his second three-run homer of the night. That gave him a career-high seven RBIs only three innings into the game. Beltran wrapped up his night with another it -- a fifth-inning single -- to give him his 21st career four-hit game.
The home runs also snapped an 11-game homerless streak for the right fielder, who entered the night in a 3-for-32 skid.
"That's what you're looking for as a hitter, going out there and feeling like you have a chance to hit the ball hard and get good results," Beltran said afterward. "I saw the ball good and made good contact and got the result I was looking for. It's not that I was looking for a homer. I was looking to hit the ball hard."
Jenifer Langosch is a reporter for MLB.com. Read her blog, By Gosh, It's Langosch, and follow her on Twitter @LangoschMLB. This story was not subject to the approval of Major League Baseball or its clubs.