The play was reviewed, but Welker was ruled to have to hit the pylon in the front left corner of the end zone.
Manning had thrown a 3-yard touchdown pass to Emmanuel Sanders with 8:29 left in the opening quarter. It was Sanders' first touchdown catch of the season and his first scoring pass from Manning.
The game marked Manning's 246th regular-season start, while Favre threw 508 touchdown passes in 302 regular-season starts for the Green Packers, New York Jets and Minnesota Vikings. Manning threw 399 touchdown passes in the regular season during his tenure with the Indianapolis Colts.
Manning had reached the 500 mark in the Broncos' 41-20 victory over the Arizona Cardinals in Week 5, a game he finished with a career-best 479 yards passing. At 38 years old, after four neck surgeries, Manning has now thrown 109 touchdown passes for the Broncos since signing with the team in 2012.
With 508 touchdown passes, Manning is currently 134 scoring passes ahead of the next active quarterback -- Drew Brees, who has 374 career scoring passes after two in the New Orleans Saints' loss Sunday to the Detroit Lions. New England Patriots quarterback Tom Brady has 372 career scoring passes.
Behind Manning and Favre, Hall of Famer Dan Marino is No. 3 all-time with 420 touchdown passes. And though current Broncos executive vice president of football operations/general manager John Elway hasn't thrown a pass since the 1998 season, he is still seventh on the all-time list with 300.
The pass to Welker gave Manning his 155th career regular-season game with at least two touchdowns. He's had 88 career games with at least three touchdown passes.
Of all of the players who have reeled in touchdown passes from Manning since the start of his rookie season in 1998, former Colts wide receiver Marvin Harrison leads the way with 112 touchdown catches, with Reggie Wayne having caught 67 scoring passes and Dallas Clark with 44.
Since Manning joined the Broncos, Demaryius Thomas leads the way with 28 touchdown catches.