Mike Hart scored on a late 11-yard touchdown run Sunday, and Adam Vinatieri kicked four field goals to give Indianapolis a 19-9 victory over Kansas City, the NFL's last unbeaten team.
It marks the first time since 1970 that no NFL team reached 4-0.
And for the first time this season, Peyton Manning failed to top 300 yards or throw for a touchdown. Manning was 26 of 44 for 244 yards with one interception. He couldn't get the Colts into the end zone until Hart's powerful win-clinching run with 4:02 to go.
Kansas City (3-1) was led by Jamaal Charles, who carried 16 times for 87 yards. Matt Cassel was 16 of 29 for 156 yards.
The Colts (3-2) have now won 17 straight at home when Manning has finished the game.
Jaguars 36, Bills 26
Tight end Marcedes Lewis caught two touchdowns passes as the Jacksonville Jaguars rallied from a 10-point deficit to beat the winless Buffalo Bills 36-26.
David Garrard shook off an interception and a lost fumble to throw for three touchdowns as the Jaguars (3-2) snapped a four-game road skid. Mike Sims-Walker's seven-yard touchdown put the Jaguars ahead for good, 27-20 lead late in the third quarter.
The Bills squandered 10-0 and 13-3 leads, and are 0-5 for only the fourth time in franchise history, the first since 1985. Buffalo has allowed 30 points in four straight games for the first time.
Falcons 20, Browns 10
Atlanta defensive end Kroy Biermann's spectacular interception return for a touchdown in the fourth quarter sent the Atlanta Falcons to a 20-10 win over the gimpy Cleveland Browns.
After pressuring Browns quarterback Jake Delhomme, Biermann leaped to deflect the pass and then made a diving headfirst catch like a seasoned wide receiver.
Matt Ryan threw a 45-yard TD pass to Roddy White as the Falcons (4-1) won their fourth straight. Michael Turner rushed for 140 yards.
The Browns (1-4) lost starting quarterback Seneca Wallace just before half with an ankle injury.
Ravens 31, Broncos 17
Ray Rice ran for 133 yards and two touchdowns, and the Baltimore Ravens frustrated Denver Broncos quarterback Kyle Orton in a 31-17 victory Sunday.
Baltimore (4-1) jumped to a 17-0 lead and coasted to its third straight win, the first this season by double digits. The Ravens moved past idle Pittsburgh into sole possession of first place in the AFC North.
The Broncos (2-3) fell to 0-5 against the Ravens in Baltimore. In those games, Denver has been outscored 142-56, including 60-24 over the last two years.
Bears 23, Panthers 6
Matt Forte rushed for 166 yards and two touchdowns, Julius Peppers had an acrobatic interception against his former team and the Chicago Bears overcame four interceptions by backup quarterback Todd Collins to beat the winless Carolina Panthers 23-6 on Sunday.
Forte scored both his TDs in the first quarter, during which Peppers silenced a booing crowd in his first game back to Carolina with a diving interception to set up a field goal.
The Bears (4-1) bounced back from an ugly loss a week earlier against the Giants to do just enough to beat the Panthers (0-5), who again couldn't move the ball with Jimmy Clausen at quarterback.
Giants 34, Texans 10
Eli Manning threw two of his three touchdown passes to Hakeem Nicks and the New York Giants held Houston to a franchise-low 24 yards rushing in a 34-10 win over the Texans on Sunday.
Osi Umenyiora sacked Texans quarterback Matt Schaub twice and also forced a fumble for the Giants (3-2). New York held NFL rushing leader Arian Foster to 25 yards on 11 carries.
Linebacker Brian Cushing made four solo tackles in his season debut for Houston (3-2). Cushing was suspended the first four games for violating the NFL's policy on banned substances.
Lions 44, Rams 6
Former B.C. Lions star Stefan Logan's 105-yard kickoff return broke a tie and the Detroit Lions rolled to a 44-6 win over the St. Louis Rams on Sunday, snapping a 10-game losing streak.
Detroit's' first victory of the year was its most-lopsided win since beating the expansion Jacksonville Jaguars 44-0 in 1995.
Logan's franchise-record tying score helped the Lions (1-4) outscore St. Louis 21-3 in the second quarter and they didn't let up.
The Rams (2-3) lost standout receiver Mark Clayton with an injured knee in the first quarter and that played a part in rookie Sam Bradford having an awful game.
Rodgers suffers concussion
The Green Bay Packers say quarterback Aaron Rodgers suffered a concussion against the Washington Redskins.
The Packers did not say exactly when Rodgers was hurt Sunday, but he did not miss any plays in Green Bay's 16-13 overtime loss to Washington.
Rodgers was slow to get up off the field after Green Bay's last offensive play, when he was intercepted by LaRon Landry.
He was 27 for 46 for 293 yards with one touchdown pass and the one interception.
Redskins 16, Packers 13
Graham Gano kicked a 33-yard field goal 6:54 into overtime Sunday, giving the Washington Redskins a 16-13 win over the Green Bay Packers.
The winning score was set up by LaRon Landry's diving interception of Aaron Rodgers at the Packers 39. The Redskins moved the ball with the help of two penalties to set up Gano's kick.
Washington overcame a 10-point fourth-quarter deficit, tying the game on Gano's 44-yard field goal with 1:07 to play. Green Bay's Mason Crosby hit the left upright from 53 yards with 1 second left in regulation.
Both teams are 3-2.
Buccaneers 24, Bengals 21
Carson Palmer's third interception gave Tampa Bay one last chance, and Connor Barth kicked a 31-yard field goal with one second left, sending the upstart Buccaneers to a 24-21 victory over the Cincinnati Bengals.
It was a signature win for young Tampa Bay (3-1), which hadn't beaten a contender. With Freeman leading the way, the Buccaneers took down the defending AFC North champions.
The Bengals (2-3) had a chance for a go-ahead field goal, but Palmer's tipped pass went to safety Sabby Piscitelli, setting up Tampa Bay's winning kick.
Titans 34 Cowboys 27
Chris Johnson scored a pair of 1-yard touchdowns in the fourth quarter, lifting the Tennessee Titans to a win over the mistake-prone Dallas Cowboys.
The Cowboys got behind 17-3 with penalties and errors on defence. Dallas managed to tie it at 17 and 20, then a tipped pass that was intercepted set up Johnson's first touchdown of the final period.
Tony Romo tied it again at 27 on a touchdown throw to Jason Witten, then offensive lineman Marc Colombo was penalized 15 yards for celebrating. Dallas (1-3) kicked off from farther back and Tennessee's Marc Mariani returned it to the 11. A penalty on the tackle moved the ball to the 5, setting up Johnson's next touchdown.
The Titans (3-2) won their 11th straight against an NFC team, the NFL's longest active non-conference win streak.
Cardinals 30 Saints 20
Max Hall's debut as Arizona's quarterback was a winning one as the Cardinals defence intercepted three passes by Drew Brees and went on to upset the New Orleans Saints.
The undrafted rookie from BYU completed 17 of 27 passes for 168 yards, Jay Feely kicked three field goals and Kerry Rhodes returned a fumble 27 yards for a score to lead the way.
Hall threw an interception that led to an early Saints field goal and fumbled twice, but both turned out to be key plays for Arizona (3-2). The first was returned 2 yards by Cardinals tackle Levi Brown for a touchdown. Guard Alan Faneca pounced on the other for a 10-yard gain.
Arizona's defence, awful in a 41-10 loss at San Diego a week earlier, converted two turnovers by the Saints (3-2) into touchdowns. Rhodes returned Ladell Betts' fumble for a score and, with 10 seconds to play, Dominique Rodgers-Cromartie returned an interception 28 yards for the game-clinching touchdown.
Raiders 35 Chargers 27
Michael Bush ran three yards for the go-ahead touchdown with 3:39 remaining and Tyvon Branch returned a fumble 64 yards for a score as the Oakland Raiders snapped a 13-game losing streak against the San Diego Chargers.
All it took to end the seven-year drought for the Raiders (2-3) was two blocked two punts, two long touchdown drives in the second half led by backup quarterback Jason Campbell and the big play at the end by Branch and Michael Huff.
This was Oakland's first win over San Diego (2-3) since September 2003 — which was the second longest active streak to Buffalo's 14-game losing streak to New England.
With the Chargers driving for the potential go-ahead score, a blitzing Huff hit Rivers just before his arm went forward, knocking the ball loose. Branch picked up the ball and raced 64 yards for the score to make 35-27 with 58 seconds left.
Eagles 27, 49ers 24
Kevin Kolb passed for 253 yards while capably filling in for injured Michael Vick, and Quintin Mikell returned Alex Smith's fumble 51 yards for a touchdown early in the fourth quarter of the Philadelphia Eagles' 27-24 victory over the winless San Francisco 49ers on Sunday night.
LeSean McCoy rushed for a score and Trevard Lindley made a last-minute interception for the Eagles (3-2), who forced five turnovers and survived San Francisco's late rally for their fifth straight win over the 49ers (0-5).
Smith passed for 309 yards, but also committed three turnovers. He received thunderous boos from the Candlestick Park crowd and an apparent tongue-lashing from coach Mike Singletary before leading two fourth-quarter TD drives.
After throwing TD passes to Vernon Davis and Frank Gore, Smith got the 49ers past midfield again in the final minute, but he was hit by Trevor Laws while making a throw. Lindley intercepted the wobbling pass with 28 seconds to play, and the 49ers dropped to their worst start in 31 years.
Kolb made his fourth career start in place of Vick, who injured his ribs in last week's loss to Washington. Kolb was the Eagles' starting quarterback out of training camp, but sat out with a concussion after the opener while Vick was chosen the NFC's offensive player of the month for September.