Justin Bethel scored the first one on a 32-yard return with 11:06 left in the quarter. It came on his first defensive snap of the season and was his first career interception. He was lined up at safety -- a new position for the gunner-turned-defensive back who worked at cornerback during the offseason -- and broke on a pass intended for Niners tight end Vernon Davis.
Four plays later, Cardinals safety Tyrann Mathieu broke on a pass intended for Anquan Boldin, picked it off and returned it 33 yards to give Arizona a 14-0 lead with 9:03 left. Mathieu added another interception in the second quarter.
Both scores were the players' first career defensive touchdowns. Niners quarterback Colin Kaepernickhadn't thrown an interception this season entering Sunday, but threw four for the day.
The Cardinals' pick-sixes are their seventh defensive touchdowns since the start of last season, most in the NFL. It was the first time since Dec. 16, 2012, that Arizona returned two pick-sixes in the same game.
According to the Elias Sports Bureau, Kaepernick is the first 49ers quarterback with two pick-sixes in a game since Steve DeBerg in Week 5 of the 1980 season (against the Rams).
Arizona romped to a 47-7 victory and improved to 3-0 on the season.