Colin Kaepernick threw for a touchdown and ran for another, while Ahmad Brooks and Donte Whitner each returned an interception for a score as the San Francisco 49ers downed the New Orleans Saints, 31-21.
Kaepernick completed 16-of-25 passes for 231 yards with the touchdown and an interception in his second career start in place of Alex Smith.
Smith suffered a concussion during the 49ers' 24-24 tie against the St. Louis Rams two weeks ago, and although Smith was cleared for contact earlier this week, Kaepernick remained the starter for San Francisco (8-2-1).
"Coach said he's going to go with who has the hot hand, so now we have two starting quarterbacks," Brooks said. "We have a guy that's 2-0, that's young, can move the pocket, move around, make plays with his feet and make plays with his arm. And Alex, who's a vet, is very savvy back there and doesn't make many mistakes. That call is going to be coach's."
Kaepernick finished with 27 yards and a touchdown on six carries and Frank Gore added 83 yards on 19 totes in the 49ers' second straight win.
Drew Brees threw for 267 yards, three touchdowns and two interceptions on 26- for-41 efficiency for the Saints (5-6), but was mainly kept in check by a 49ers defense that racked up five sacks.
"I felt like we played well enough to win in a lot of areas today," Brees said. "What's glaring is the two turnovers that resulted in touchdowns for them. That can't happen."
Marques Colston became the Saints' all-time leader in touchdowns and finished with 36 yards and a score on four receptions as New Orleans had its three-game win streak snapped.
The 49ers received the ball to start the second half with the game tied at 14-14, and Kaepernick converted a 3rd-and-2 with a 45-yard strike to Delanie Walker near the left sideline before Kendall Hunter's 21-yard run set up a 6- yard touchdown grab by Gore.
Then two plays into New Orleans' ensuing drive, Whitner intercepted a high pass from Brees that tipped off the hands of a leaping Colston and took it 42 yards down the left sideline for a touchdown and a 28-14 lead with 11:30 left in the third quarter.
The Saints responded with an 8-play, 80-yard scoring drive to get back within a touchdown as Lance Moore fought off a defender and hauled in a 43-yard reception to move the ball to the San Francisco 10, setting up Jed Collins' 2- yard touchdown grab.
San Francisco regained its two-possession advantage with a 16-play, 85-yard drive that stretched into the fourth quarter and ate up nearly 9 1/2 minutes of clock.
Kaepernick converted three third downs through the air in the march, including a 3rd-and-11 at the 49ers 35-yard line, but the drive stalled inside the Saints 10 and San Francisco was forced to settle for David Akers' 27-yard field goal for a 31-21 lead with 7:50 left in the game.
The Saints would not threaten for the remainder of the contest and after failing to convert a 4th-and-4 at their own 46, San Francisco was able to run off all but 1:05 of game clock as Akers' 33-yard field-goal attempt was blocked.
New Orleans then advanced as far as the San Francisco 37 before Brees took a knee to run off the final second of play.
San Francisco took over on offense at its own 38-yard line after the teams traded punts over the first three possessions of the game, and Mario Manningham's 40-yard catch-and-run on the second play of the drive moved the ball deep inside Saints territory before Kaepernick capped the quick, 4-play march with a 7-yard rush off left end for a touchdown.
The Saints answered with a 10-play, 79-yard trek Joe Morgan highlighted with a diving, 33-yard reception before David Thomas finished off the drive with a 6- yard touchdown grab, tying the game at 7-7 with 1:45 left in the first quarter.
New Orleans moved the ball as far as the San Francisco 39 on its next touch, but Brees was called for intentional grounding on a 3rd-and-10 to force a 4th- and-30.
Ted Ginn Jr. then muffed the ensuing punt and the Saints recovered the ball at the 49ers 11. Two plays later, Brees found Colston in the back of the end zone for a 10-yard score and a 14-7 advantage.
Colston's TD reception was the 56th of his career, surpassing Deuce McAllister's franchise record.
Kaepernick was later intercepted by Patrick Robinson within the final minute of the second quarter to set the Saints up at their own 44 with a chance to add to their lead before the half, but Brooks stepped in front of a Brees pass over the middle two plays later and returned it 50 yards for a touchdown to make it a 14-14 game at the break.
Brees has now thrown a touchdown pass in 54 straight games, extending his own record. He fell to 5-1 against the 49ers in the regular season ... The game was a rematch of last season's NFC divisional playoff game, which the 49ers also won, 36-32 ... San Francisco leads the all-time series between the teams, 46-24-2 ... Walker ended with a game-high 81 yards on three catches ... The Saints went 3-for-11 on third downs, while San Francisco converted 6-of-13 third-down opportunities.