With both Alex Smith (49ers) and Jay Cutler (Bears) sitting out due to concussions, the second-year Kaepernick rose to the occasion in his first NFL start by tossing two touchdown passes.
The young quarterback led the 49ers to a 20-0 lead at half-time and never took his foot off the gas.
"We didn't know if it was going to be (Smith) or me (starting), it's just great to be on the field," Kaepernick said. The decision on who was starting was not officially announced until early on Monday.
"I wasn't really nervous, I've had a lot of time in this offense. It's everything I could've wished for."
Things did not go smoothly for Bears' back-up Jason Campbell, who was sacked six times and intercepted twice in the game at San Francisco's Candlestick Park.
The Bears trailed 27-0 before Brandon Marshall caught a 13-yard touchdown pass in the third quarter for the team's only score. Chicago's (7-3) second straight loss dropped them into a tie with Green Bay for first in the NFC North.
Kaepernick finished with 243 yards passing and no turnovers and San Francisco (7-2-1) added 123 yards on the ground to extend their lead in the NFC West.
49ers tight end Vernon Davis caught a touchdown pass in the first half while Kendall Hunter ran in a 14-yard score.
Michael Crabtree caught a 10-yard touchdown pass in the third before San Francisco buried the Bears in the fourth with a second David Akers field goal and then forced a safety.
Kaepernick's performance at quarterback may have created a dilemma for the 49ers when Smith returns.
"We'll make that decision as we go forward," said 49ers coach Jim Harbaugh. "I tend to go with the guy that's got a hot hand and we've got two quarterbacks that have got a hot hand."
Chicago was badly in need of a hot hand as they finished with just 143 total yards. Campbell threw for only 107.
"It's tough. This definitely wasn't the way we prepared all week to come out and give this type of performance," Campbell said. "Give their defense credit, but it definitely wasn't our best effort."
