Derek Anderson threw for 310 yards and a pair of scores to lead a potent offensive attack. The Browns picked off Eli Manning three times on the way to a 35-14 thrashing of the New York Giants, handing the defending Super Bowl champions their first loss of the season.
Eric Wright had the backbreaking interception for the Browns, returning the ball 94 yards for a score with 8:07 remaining in the final quarter.
Anderson completed 18 of 29 passes with his main target being Braylon Edwards, who caught five balls for a career-high 154 yards and a score. Jamal Lewis rushed for 88 yards and a touchdown.
The Browns (2-3), who were coming off their bye week after beating Cincinnati on Sept. 28, racked up 454 yards of offense and didn't punt the entire game. They had four touchdowns for the season coming into the contest, but they equaled that total Monday by using a dominating offensive line.
"I felt against Cincinnati we started to move the ball," said Anderson. "The biggest thing is when they brought pressure, we saw it and I was able to get the ball out. Once they switched into coverage, we were able to run the ball.”
Manning, the reigning Super Bowl MVP, completed 18 of 28 passes for 196 yards with a score for New York (4-1), which had won its previous 12 games outside Giants Stadium. Derrick Ward ran for 101 yards for the Giants, while Brandon Jacobs added 67 yards and a TD on the ground in defeat.
"I'm disappointed," said Manning. "We didn't come out and play the way we've been playing. You turn the ball over three times. That's just not the formula for winning."
The Giants' loss leaves Tennessee as the lone remaining unbeaten team in the league this season.
"We make no excuses," said Giants coach Tom Coughlin. "It was a physical game and we lost the battle of turnovers."
Already ahead by three points at the half, the Browns took advantage of a turnover to expand the lead to 20-14. Manning tried to go deep on the first play of the half, but Brandon McDonald came up with the interception, setting the Browns up at the New York 46.
Jerome Harrison ran 33 yards on a reverse to help set up Phil Dawson's 26-yard field goal.
Cleveland's offensive line then took command as the Browns held the ball for better than eight minutes before Edwards capped a 14-play, 87-yard drive with an 11-yard touchdown catch on the left side of the end zone on the first play of the final quarter.
Edwards was able to get open because corner back Aaron Ross fell down and was injured on the play.
Manning drove the Giants from their own 14 to the Cleveland nine, but Wright stepped in front of Amani Toomer and darted down the sideline to the end zone. The Browns got the two-point conversion too, with Edwards making the catch.
The Giants turned the ball over on downs and the Browns ran out the final 3:58.
The Browns received the opening kickoff and Anderson's 49-yard connection to Edwards on 3rd-and-4 moved the ball to the Giants' 25. The Browns got as far as the 11, but the march stalled and Dawson kicked a 28-yard field goal.
Manning was then picked off by Brodney Pool at the Cleveland five, and the Browns moved the ball from their own 29 to the Giants' 34, but Dawson's 51-yard field goal try was wide left.
The Giants then needed just six plays to get to the end zone, with Jacobs powering off left tackle from seven yards away, plowing over safety Mike Adams with 12:09 remaining in the half.
On the ensuing play from scrimmage, Edwards got behind Ross for a 70-yard gain to the New York four. Two plays later, Lewis bounced to the right side for a TD run and a 10-7 lead.
After a punt, the Browns scored again, this time on Anderson's 22-yard connection to Darnell Dinkins in the middle of the end zone, as the pass was barely over the head of linebacker Antonio Pierce.
The Browns appeared to get a big break in the final minute of the half, as Manning was sacked on third down and fumbled the ball away at the Cleveland 21. Adams, though, was called for illegal contact, giving the Giants a fresh set of downs.
Three plays later, Manning hit Plaxico Burress for a three-yard score in the left side of the end zone with 12 seconds remaining to complete the 80-yard drive and bring the Giants within 17-14.