Luck threw a career-high five touchdown passes and topped 300 yards for the 10th time this season, a franchise record, helping the Colts improve to 8-4.
Luck finished 19-of-27 for 370 yards, but was not the only quarterback on the field enjoying a big day.
Colt McCoy, replacing Robert Griffin III, was 31-of-47 for 392 yards and three touchdowns for Washington.
Philip Rivers’ one-yard pass to Eddie Royal with 38 seconds to go saw the San Diego Chargers beat the Baltimore Ravens 34-33 to move to 8-4.
The Chargers came from 30-20 down in the final 6:13 of the game. It was Baltimore’s first home loss since 2009.
Drew Brees threw five touchdown passes to lead the New Orleans Saints to a 35-32 win over the Pittsburgh Steelers. The win ended a three-game losing streak for New Orleans as they moved to 5-7.
The St Louis Rams scored 38 points in the first half alone on their way to a 52-0 rout of the Oakland Raiders, who suffered the second-biggest defeat in franchise history.
There was a changing of the guard as Johnny Manziel replaced Brian Hoyer at quarterback for the Cleveland Browns, but he could not prevent a a 26-10 loss to the Buffalo Bills.
Manziel, limited to the occasional snap until now, marked his first appearance of any significance with a touchdown but, having entered with the team trailing 20-3, could not spark a full comeback.
The Jacksonville Jaguars came from 21-0 down to beat the New York Giants 25-24 and record only their second win of the season to pile pressure on New York coach Tom Coughlin.
The Giants built a big lead in the second quarter but Jacksonville’s defence led the second-half recovery, with JT Thomas recovering an Eli Manning fumble in the endzone before Aaron Colvin returned another turnover for a score in the fourth.
Ryan Fitzpatrick’s franchise-record six touchdowns led the Houston Texans to a 45-21 win over the Tennessee Titans.
The Cincinnati Bengals won ugly to stay top of the AFC North as they beat the Tampa Bay Buccaneers 14-13 in Florida.
Andy Dalton ran in the first touchdown from five yards before throwing a 13-yard pass to AJ Green for the second in the third quarter.
The Carolina Panthers slumped to a sixth straight loss as the Minnesota Vikings returned two blocked punts for touchdowns in a 31-13 win.
Adam Thielen and Everson Griffen each scored from the punts while Teddy Bridgewater threw for two touchdowns.
Aaron Rodgers won the battle of the star quarterbacks against Tom Brady as the Green Bay Packers claimed their fourth win in a row by edging out the New England Patriots 26-21.
Both teams have been tipped as Super Bowl contenders, but it was the Packers who claimed the bragging rights in this encounter, Rodgers throwing for two touchdowns as the Patriots’ seven-game winning streak was ended.
Peyton Manning starred for the Denver Broncos as they beat the Kansas City Chiefs 29-16 to stay a game ahead of San Diego in the AFC West.
The veteran quarterback threw for two touchdowns while Connor Barth was five from five for field goal attempts as Denver beat the Chiefs for the sixth time in a row.
Julio Jones caught 10 passes for 189 yards and a touchdown as the Atlanta Falcons claimed a 29-18 win over the Arizona Cardinals.