Kaepernick went 19-of-28 passing and Anquan Boldin made nine catches en route to 98 yards for the 49ers (8-4), who tightened their grip on the NFC's final wild card playoff spot.
Vernon Davis picked up 82 yards with a touchdown on four receptions.
On defense, San Francisco put consistent pressure on the Rams' Kellen Clemens, who completed just 19-of-37 throws for 218 yards with a TD and an interception.
Zac Stacy compiled 72 rushing yards on 19 carries for St. Louis (5-8).
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