GLENDALE, Ariz. -- The Arizona Cardinals dominated another opponent on Sunday, and the San Francisco 49ers had another long afternoon.
Especially Colin Kaepernick.
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Carson Palmer threw for 311 yards and Arizona returned two of Kaepernick's first four passes for touchdowns and the Cardinals romped past the San Francisco 49ers 47-7.
Larry Fitzgerald caught nine passes for 134 yards and two touchdowns and Chris Johnson rushed for 110 yards and two scores for the Cardinals (3-0), who won at Chicago 48-23 last week.
It's the first time the franchise has had two 40-point victories in a row since 1969 and its largest margin of victory since a 44-0 win over Houston in 1970.
Kaepernick threw a career-worst four interceptions, two by Tyrann Mathieu, and finished 9 for 19 for 67 yards, a quarterback rating of 16.7.
Justin Bethel returned the first one 21 yards for a touchdown and Mathieu ran untouched 33 yards for another score.
Kaepernick had a 12-yard TD run for San Francisco (1-2).
The Cardinals scored 24 points off the four interceptions and opened an early two-game lead in the NFC West.
Palmer won his ninth in a row, the NFL's longest active streak, and is 16-2 in his past 18 starts.
Palmer completed 20 of 32 passes and threw his first interception of the season.
The defense scored three times, the last when Kevin Minter tackled Carlos Hyde for a safety.
Arizona had 446 yards to 156 for the 49ers, coming off a 43-18 loss at Pittsburgh.
Kaepernick's first pass, on third-and-13 from the San Francisco 12-yard line, was intended for Vernon Davis, but Bethel stepped up to grab it and run untouched to the end zone. The pick for Bethel, a two-time Pro Bowl special teams player, came on his first play from scrimmage this season.
After the subsequent kickoff, again on third down, Kaepernick tried to get a sideline pass to Anquan Boldin. Mathieu stepped in front of the intended receiver, caught the ball then ran 33 yards for the score, high-stepping the final 10.
On Arizona's next possession, consecutive passes of 23 and 11 yards to Fitzgerald, led to Johnson's 6-yard burst up the middle on the second-quarter's opening play and it was 21-0.
Fitzgerald's performance came a week after he caught eight passes for 112 yards and three touchdowns in Chicago.
Palmer threw his first interception of the season late in the second quarter, and San Francisco quickly gave it back.
Kaepernick threw deep, intended for Davis, but Mathieu got to it first.
The "Honey Badger" returned it 17 yards, leading to Chandler Catanzaro's 22-yard field goal that made it 31-7 as the half ended. It is the only time in 12 red zone appearances this season that Arizona has not scored a touchdown. After the interception, Mathieu ran to the stands and handed the ball to a small boy, who gathered it in both arms.