The crowd at Busch Stadium gave Molina a standing ovation when he walked in from the bullpen after pregame warm-ups and another cheer before he batted in the first inning.
"He's probably one of the toughest guys I've ever seen in the big leagues," general manager John Mozeliak said before the game. "He looks great."
Molina, 32, tore a ligament in his right thumb sliding into third base July 9 and underwent surgery two days later. He missed seven weeks, beating the original prognosis of eight to 12 weeks and perhaps the rest of the season.
"I feel good, 100 percent good," Molina said before the game. "Every part of my body feels great, and I'm ready to go."
Bringing him back so quickly is a bit of a gamble, but Molina passed every test.
"We are doing it with a little bit of caution or holding our breath to some degree," Mozeliak said. "But he feels like he can protect himself to allow himself to contribute. He really wants to be out there."
Outfielder Shane Robinson, who was placed on the DL on Tuesday, underwent season-ending arthroscopic surgery on his left shoulder Thursday. Manager Mike Matheny said it will be a month before Robinson can begin rehab.
Molina was batting .287 with seven homers and 30 RBIs in 83 games and was voted the starting catcher on the National League All-Star team. He was 5-for-6 with three doubles and two RBIs in two rehab games at Double-A Springfield.
Molina is a big upgrade defensively, lauded for game management in addition to an arm that's perhaps the best in the majors.
"Yaddy has a reputation, and they know he'll pick them off if they get too far off," Matheny said. "And if they don't get a good jump and the pitcher doesn't give them much of a chance, they're not going to have much of a shot. He's a prolific throw in my opinion, and I think he's proven that every year."
Cruz, batting .195 with 12 RBIs in 44 games, was optioned to Springfield and will return when rosters expand on Sept. 1. The 37-year-old Pierzynski, batting .265 in 21 games with four homers and 31 RBIs, will be the backup.
Molina was being eased back, to a degree. He has batted fifth 71 times but was one slot behind Jhonny Peralta.
The Cardinals also plan to recall left-hander Marco Gonzalez from Triple-A Memphis and add him as the 26th man for a day-night double-header Saturday. The 22-year-old first-round draft pick in 2013 is scheduled to start the second game.
Gonzales has pitched at all four levels this season, including three starts with St. Louis.
The Associated Press contributed to this report.