He managed to escape a sack attempt on a TD drive in the first quarter, had two long runs and was sharp all game throwing the ball against the 49ers (5-3), who lost their third straight game.
Burrow went 28 for 32 for 283 yards and ran for 43 more against a Niners defense that has uncharacteristically struggled in recent weeks.
Burrow helped Cincinnati take control of the game early in the fourth quarter after Logan Wilson intercepted a pass from Purdy. The Bengals struck on the next play when Burrow lofted a 17-yard TD pass to Ja’Marr Chase to make it 24-10.
Purdy had thrown an interception on the previous drive in the red zone to Germaine Pratt, giving him five interceptions in the past three games after having none in the first five.
Purdy, who played despite being in concussion protocol during the week, threw for 365 yards and had a TD pass to Christian McCaffrey on the drive after his back-to-back interceptions.
But Burrow responded with two long passes to Trenton Irwin and Chase and two first downs running to set up Joe Mixon’s 5-yard run with 2:54 left for the Bengals.
Purdy lost a fumble on a strip-sack to Trey Hendrickson to seal the loss for the 49ers, who have been held to 17 points or fewer in three straight games for the first time since Kyle Shanahan’s first season in 2017.
Burrow and the Bengals started fast as he connected on TD passes to Tyler Boyd and Andrei Iosivas on the first two drives of the game to take a 14-7 lead.
Cincinnati had chances to add to the lead but Evan McPherson missed a 50-yard field goal following a third-down sack and Irv Smith lost a fumble at the 49ers 5 late in the half to keep it 14-10.
Bills at Bengals, 8:20 p.m., NBC, 700, 1530, 102.7, 104.7