Pujols launched a slider from former teammate Johan Oviedo over the Big Mac Land sign in left field at Busch Stadium, his 22nd homer of the season. The solo drive in the fourth inning made it 1-all.
Pujols faced Oviedo for the first time and made the 24-year-old righty the 456th different pitcher he has homered against.
"It was a good pitch to hit and I just put the best swing on the night on it,'' Pujols said. "That was it. A 1-2 count, just not trying to do too much.''
The St. Louis star hadn't homered in a week since hitting No. 699 and 700 at Dodger Stadium last Friday. Pujols had gone 10 at-bats without a home run after two starts and one pinch-hit appearance.
The Busch Stadium crowd gave the 42-year-old Pujols a long standing ovation before he came out of the Cardinals dugout to tip his cap for a curtain call.
"It's pretty awesome,'' Pujols said. "I didn't know it was going to be like this. It's pretty good just to be embraced like this. I mean this is what I've been getting all year long but today was extra special. It was a great night overall.''
Before the game, the slugger was recognized for hitting his 700th last week at Los Angeles. He was given a gold-plated, engraved bat by owner Bill DeWitt Jr., team president Bill DeWitt III and manager Oliver Marmol.
Pujols' homer was his 55th against the Pirates, his third most against any team, trailing Houston (70) and the Chicago Cubs (62).
Pirates manager Derek Shelton took a moment to appreciate Pujols' accomplishments.
"I think we're seeing one of the best hitters of our generation and he's had an unbelievable second half,'' Shelton said. "You cannot make mistakes to him right now. We made the one mistake to him and he hit it out of the ballpark. What he's done over the course of his career and especially what he's done over the second half is extremely special."
Pujols is fourth on the career home run list behind Barry Bonds (762), Hank Aaron (755) and Babe Ruth (714).
The Associated Press contributed to this report.