Peyton Manning broke the NFL record for most career touchdown passes and guided the Denver Broncos to their fifth win of the season as they hammered the San Francisco 49ers 42-17 in their clash at Sports Authority Field.

The 38-year-old got his side on the scoreboard in their first drive of the game when he fired to Emmanuel Sanders over the middle of the endzone for a three-yard score.

Manning spread the ball out well to his receivers and notched his second strike of the game when he looped a pass to Wes Welker, who sprinted and then dived to the pylon for a 39-yard touchdown.

The 49ers tried to hit back but Anquan Boldin produced a costly drop in the endzone, and forced his side to settle for a field goal from the boot of Phil Dawson.

Manning made history when he threw the 509th touchdown pass of his career, breaking Brett Favre's record, as he found Demaryius Thomas for an eight-yard strike on an out route in the endzone.

San Francisco fought back just before the break when Colin Kaepernick moved his side downfield with precision, and then drilled the ball to Stevie Johnson at the back of the endzone.

In the second half, a costly mistake by Kaepernick put the Broncos in prime position to extend their lead as his pass was picked off by Aqib Talib. Manning took full advantage as he fired deep to Thomas for a 40-yard touchdown.

John Fox's side took complete control of the game when Ronnie Hillman found space through the middle of the line and ran all the way to the endzone without being touched for a 37-yard score.

Late in the third quarter, Hillman put the game beyond doubt after Manning moved his side to the goal line with another excellent series of throws, and that allowed the back to power over for the score.

The 38-year-old was pulled from the game in the fourth quarter with the result beyond doubt at 42-10. The 49ers managed to get a consolation touchdown when backup Blaine Gabbert fired to Bruce Ellington for a walk-in touchdown, but the night belonged to the Broncos and Manning.