Manning regained his record with 51 when he threw for 400 yards and four touchdowns, including three in the fourth quarter. He surpassed the 50 TD passes Tom Brady threw in 2007 and led the Broncos (12-3) to a 37-13 win over the Texans (2-13) that extended Houston's franchise-record skid to 13 games.
Manning did it on a 25-yard pass to Julius Thomas with 4:28 remaining. Just 2 ½ minutes earlier, he tied the mark with a 20-yard pass to Eric Decker.
He entered the game with 47 and his first touchdown came on a 36-yard pass to Demaryius Thomas in the second quarter. The second was a 10-yard throw to Decker earlier in the fourth period.
Manning had previously established the record by throwing 49 touchdown passes in 2004.
The Broncos already had a spot in the playoffs, but their victory, combined with Kansas City's loss to Indianapolis, gave them the division crown. They could secure home-field advantage throughout the playoffs if New England doesn't win its late game at Baltimore.
Matt Schaub started for the first time since Oct. 13 in place of an injured Case Keenum. He finished with 176 yards and one touchdown with two interceptions for the Texans.
The Broncos couldn't do anything offensively in the third quarter, gaining just 38 yards, and had to punt on each of their four possessions. Their defense helped them out after that, with Mike Adams intercepting Schaub at the Houston 28.
Manning wasted no time making Houston pay, and found Decker two plays later for the touchdown that extended the lead to 23-13.
It was all Broncos after that, with Manning grabbing the record with two more touchdown passes.
Manning made the record-setting throw to Thomas and walked toward the end zone, where his teammates patted him on the head. He then took off his helmet and walking to the sideline and pumped his fist once. His teammates came out to greet him and he gave dozens of high-fives as he grinned and walked to the bench.
Decker somehow got the ball after the touchdown and tucked it in the side of his jersey, where it remained as he walked off the field.
Decker led the Broncos with 10 receptions for 131 yards, and Demaryius Thomas had eight catches for 123 yards. Wes Welker missed his second straight game after sustaining his second concussion in four weeks on Dec. 8. Schaub found Keshawn Martin on a 15-yard touchdown pass to get Houston within 16-13 early in the third quarter. Andre Johnson dropped a pass in the end zone on the play before. Rookie tight end Ryan Griffin had a 40-yard reception early in that drive.
Johnson finished with four catches for 63 yards. He has 103 catches this season to reach 100 for the fifth time in his career, tying an NFL record for most seasons with at least that many receptions.
Johnson entered the game needing one catch to reach the mark held by Welker. He did it on a 33-yard reception in the first quarter. Johnson also had more than 100 receptions in 2006, 2008, 2009 and 2012.
Manning's TD pass to Demaryius Thomas on the first play of the second quarter put Denver up 10-3. Houston used a 35-yard field goal to cut the lead to 10-6 after a 51-yard punt return by Martin.
Matt Prater made field goals of 25 and 44 yards to extend Denver's lead to 16-6 at halftime.
The Broncos lost star linebacker Von Miller to a knee injury in the first quarter, and Houston cornerback Johnathan Joseph went out with a foot injury in the second quarter and didn't return.
Manning's record chase
Manning entered the game with 47 TDs and his first touchdown came on a 36-yard pass to Demaryius Thomas in the second quarter. The second one was a 10-yard throw to Decker early in the fourth period.
Brady set the record, which previously belonged to Manning, in 2007. Manning had established the record by throwing 49 touchdown passes in 2004.
Surrounded by the best targets he's ever had, operating a turbocharged assault with a body that's much less a question mark, Manning is putting up record numbers like he did in that remarkable 2004 season.
That year, Marvin Harrison, Reggie Wayne and Brandon Stokley all topped 1,000 yards receiving. Manning established NFL records with 49 touchdown throws and a 121.1 passer rating, marks since surpassed by Brady and Aaron Rodgers (122.5).
Manning was the NFL's 2012 Comeback Player of the Year, showing he was every bit as good as before. He's having his best season at age 37, just two years removed from the four neck surgeries that weakened his right triceps and threatened his career. He hadn't missed a start with the Colts before 2011.
Last week, Houston interim coach Wade Phillips said Manning's season was "just the best year ever of any quarterback."
Manning began 2013 by becoming the first quarterback since 1969 to throw for seven touchdowns in a game. Earlier this month he broke an NFL record he held with Brett Favre for most playoff appearances when he qualified for his 13th trip to the postseason.
Although he could set several more standards this season, Manning has insisted his only concern is the Broncos' win-loss record. He wants desperately to gain home-field advantage and the top seed in the AFC playoffs again.
Manning finished Sunday's game with a career-high 5,211 yards passing. He is 266 from surpassing the single-season record for yards passing set by Drew Brees in 2011.
Manning threw 37 touchdown passes last year, which broke a franchise record of 27 set by John Elway in 1997 and tied by Jake Plummer in 2004.
Sports Director Greg Bailey and Spencer Tillman will wrap up today's game on "Inside the Game," tonight at 10:35pm.