The Rams (1-3) had an overtime win and tie against San Francisco last year, and took the early lead Thursday before falling flat. Greg Zuerlein banged in a 40-yard field goal off the right upright to end a nine-game scoring drought in the first quarter, but the 49ers answered with 28 straight points.
"Tomorrow's going to be a pretty tough day in the film room," Rams quarterback Sam Bradford said. "The good news is we have 10 days, 11 days until we play again and there's going to be ample time to get that corrected."
St. Louis was held to 188 total yards and was completely stuffed on the run, with 18 yards on 19 carries.
"That's what we do," said safety Donte Whitner, who had an interception in the end zone. "We stop the run first, then we stop the pass and then we get away with wins."
The 49ers came close to a Super Bowl title in February and regained their footing against the team that gave them the most trouble last season. Minus cornerback Nnamdi Asomugha and linebackers Patrick Willis and Aldon Smith, they quieted a raucous, hopeful crowd, sending all but a few thousand home early.
"We're going to have to get tough in here," Rams defensive end Chris Long said. "We're going to have to hold each other accountable and make plays and dig our way out of this hole because nobody's going to do that for us."
Kaepernick had no touchdown passes and four interceptions the previous two weeks and completed fewer than 50 percent of his passes. He was 15 for 23 for 167 yards.
Boldin had a monster debut with the 49ers after helping the Ravens beat San Francisco in the Super Bowl, but had been quiet along with the rest of the offense the previous two weeks. He had two highlight catches in the second quarter, a 42-yarder despite Cortland Finnegan getting flagged for holding, and a 20-yard score capped by a dive into the end zone after barely avoiding the sideline.
Gore was the second straight back to burn the St. Louis defense, with DeMarco Murray gaining 175 yards in Dallas' 31-7 win Sunday.
"It's disgusting," Long said. "It really is just disgusting."
The Rams have trailed by double digits in every game, making up an 11-point deficit against Arizona in the opener but not gaps of 21 and 24 points against Atlanta and Dallas, and were down by 25 in the fourth quarter against San Francisco.
They got hit by injuries, too, the worst of them when rookie safety T.J. McDonald was carted off with a leg injury in the second half.
Bradford was 19 for 41 for 202 yards and an interception and has been sacked 11 times the last two games after the Rams allowed none the previous four games.
After mustering just 25 yards in the first quarter, the 49ers took a noisy crowd out of it in the second, averaging more than 11 yards per snap while piling up 176 yards and two touchdowns. Kaepernick was 8 for 12 for 104 yards in the half, all but 11 of those yards in the second quarter.