But he still hasn't beaten the Seattle Seahawks.
He can change that Sunday against the team that has handed Kaepernick the two most lopsided losses of his starting career.
Russell Wilson has outplayed Kaepernick both times in the budding competition between two of the NFL's most dynamic young quarterbacks who lead the way in the rivalry between the NFC West's top two teams.
But Kaepernick has something more pressing on his mind this week than any individual comparisons or matchups with Wilson.
"I don't worry about things like that," he said. "I'm worried about the next game that's on our schedule."
That's Sunday when Seattle comes to town for a game the 49ers (8-4) have to win to prevent the Seahawks (11-1) from ending San Francisco's two-year run as NFC West champions.
Seattle can clinch its first division title since 2010 with a victory.
The 49ers got good news Friday when Pro Bowl left tackle Joe Staley (sprained knee) practiced for the second consecutive day and said he "fully expects to play" against Seattle.
Staley said Friday it would take more than a sprained knee to keep him out against the Seahawks.
"It's just intense," Staley said. "We don't like them. They don't like us. I don't have a magic answer for why it's so intense, but it's a physical game every time we play. There's some bad blood there, and it's gotten worse for a variety of things."
The similarities between Kaepernick and Wilson have become a sideshow to the rivalry between two of the NFL's top teams.
Both players have strong throwing arms and present a dual threat with their ability to run and escape from the pocket.
Wilson ranks third among quarterbacks with 456 yards rushing and Kaepernick is fifth with 376 yards. Both rank among the league's top 10 in average yards per pass play.
"They're two great young quarterbacks, both very talented," 49ers coach Jim Harbaugh said. "They stand in there and deliver."
Wilson has done that better so far in the head-to-head matchups between the two quarterbacks.
Wilson threw four touchdown passes in Seattle's 42-13 rout of the 49ers last December in Seattle. He then had one TD pass and 33 yards rushing as the Seahawks topped San Francisco again 29-3 on Sept. 15. Kaepernick had a career-high three interceptions and a career-low 20.1 passer rating in the latter game at Seattle.
The 49ers expect Kaepernick to bounce back in Sunday's rematch against the only team he has a 0-2 record against since he took over as San Francisco's starter midway through last season.
"He might come out and break records, have one of the best games of his life," said tight end Vernon Davis, who has caught 10 of Kaepernick's 15 touchdown passes this season.
"You never know what could happen in this game. I know Colin, and he's one of those guys that's going to go out and play his hardest no matter what. He's man enough to take criticism, he owns up to his mistakes and he's a winner."
After an auspicious debut as a starter last season, when he helped take San Francisco to the Super Bowl, Kaepernick has taken his share of criticism this season for a team that ranks 31st in the NFL in passing offense.
Meanwhile, Wilson has blossomed into the league's third-ranked quarterback with a passer rating of 108.5 and has drawn NFL MVP consideration.
Kaepernick had 127 yards passing against Seattle in September and just 91 and 127 yards through the air in back-to-back losses to Carolina and New Orleans in November.
But he responded with three touchdown passes the next week against Washington and had 275 yards passing during last week's 23-13 victory over St. Louis — his most since beginning the season with a career-high 412 yards passing in a win over Green Bay.
That has helped push Kaepernick's passer rating up to 88.9 after it fell to a career-low 72.5 earlier this season. He's completed 57.8 percent of his passes for 2,312 yards this season.
"He's done an outstanding job," offensive coordinator Greg Roman said. "I thought last week's game against the Rams was one of the best games, if not the best, he's played big-picture wise. Everything from soup to nuts, A to Z, I thought it was a magnificent performance on a lot of levels."
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