With one out in the sixth inning, Pujols, 42, swung at the first pitch from reliever Raynel Espinal, an 84 mph slider, and launched a 427-foot shot out to left field. The two-run shot on Friday tied the score at 4-4.
The crowd was already on its feet in anticipation, and Pujols rounded the bases to a tremendous cheer.
"I was just looking for a good pitch to hit," he said. "I put the best swing on the night [on it]. Actually ... my last one I thought was gone, too, but obviously as you guys know this place, this place is tough."
Pujols was referring to a deep fly ball in the seventh that was caught at the warning track, just missing No. 699. According to ESPN Stats and Information, the ball would have been out in 12 other ballparks.
Pujols is fourth on the all-time home run list, trailing only Barry Bonds (762), Hank Aaron (755) and Babe Ruth (714).
His second-half homers have coincided with his team's surge in the standings. The Cardinals, who at the All-Star break were a half-game behind the Milwaukee Brewers for first in the NL Central, now lead the division by 7 1/2 games.
"All of his homers are meaningful right now," Cardinals manager Oliver Marmol said.
Friday night's homer, which had an exit velocity of 106.3 mph, was Pujols' 19th of the season, the second-most in a season for a player 42 years or older. He has 12 home runs since Aug. 10, one behind Aaron Judge and Eugenio Suarez for the most in MLB over that span.
"Right before the All-Star break I started swinging the bat well," Pujols said. "Earlier in the year, I was hitting the ball hard, just no luck. I was hitting the ball over 100 mph and right at people. You get frustrated. You have to keep trusting the process and hard work and know it's going to turn around.
"If it doesn't turn around you're in trouble. Things have turned around in my favor. I thank God for that."
Pujols has a six-game RBI streak, his longest since 2017. He upped his career total to 2,203 RBIs, moving him within 11 of Ruth for second all time. Aaron holds the record at 2,297.
"It'd be one thing if he's just chasing it, but the thing is, he's taking an unbelievable approach and delivering when we need it most," Marmol said.
The home run overshadowed Cardinals reliever Ryan Helsley's ninth inning, when he struck out three Reds batters on nine pitches to achieve the sixth immaculate inning in MLB this year.
Pujols isn't likely to start both ends of a doubleheader on Saturday as the Cardinals have three home games left before a West Coast trip. Huge crowds, including over 47,000 on Friday, have come out all week to see him. He didn't disappoint as he inched another homer closer to the 700 club.
"I'm just so thankful and grateful and blessed to be back here and finish my career where it started," he said.
"And having a great year."