Anderson was 18-for-29 for 310 yards and did not throw an interception
The Cleveland Browns ended the New York Giants' unbeaten start to the season with a 35-14 home victory over the defending Super Bowl champions in Ohio.
Derek Anderson threw two touchdown passes and an Eric Wright touchdown with eight minutes left sealed victory.
Wide receiver Braylon Edwards said the win had given Cleveland "new life" after the Browns had started the season with three straight defeats.
"We're 2-0 in a 14-games season. Everything looks better now," he said.
New York had won 12 successive games away from New Jersey, including last year's surprise Super Bowl triumph, with their last defeat on the road coming in the opening week of last season.
But Monday's defeat means the Giants' lead over Washington and Dallas in the NFC East has been cut to just half a game.
Eli Manning was intercepted three times and the Giants could not contain Cleveland's offence, leaving the Tennessee Titans as the only unbeaten team in the NFL.
Much of the praise was reserved for Anderson, who did not throw an interception and tossed touchdown strikes to Darnell Dinkins and Edwards. Jamal Lewis rushed for the other Cleveland touchdown and Phil Dawson kicked a pair of field goals.
"Anderson played like the best quarterback in the league," added Edwards. "We had some guys coming back from injuries too and that made a big difference."
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Highlights: Chargers v Patriots
Other NFL matches produced a flurry of frenetic endings, with Arizona scoring a touchdown off a blocked punt to secure a 30-24 overtime victory over Dallas on Sunday.
It was the first time in NFL history that an overtime game had ended with a blocked punt leading to a touchdown.
Monty Beisel scored for Arizona, who had led by 10 points with three minutes remaining in regular time.
"I can't remember a game that was this crazy, especially towards the end," Arizona quarterback Kurt Warner said.
"That topped off an incredible game," Beisel said. "Special teams stepped up and we made the difference."
Warner threw for 236 yards with two touchdowns and an interception, while Dallas counterpart Tony Romo threw for 321 yards and three scores and Nick Folk hit a game-tying 52-yard field goal for Dallas to force overtime.
There was a setback for the Cowboys' NFC East rivals Washington as St Louis's Kris Brown nailed a 49-yard field goal as time expired to give the Rams their first victory of the season, a 19-17 triumph over the Redskins.
In Minneapolis, Ryan Longwell kicked a 26-yard field goal with nine seconds left to lift Minnesota to a 12-10 victory over Detroit.
And Atlanta's Jason Elam kicked a game-winning field goal as time expired to give the Falcons a 22-20 victory over Chicago.
The Houston Texans narrowly nabbed their first win of the season as Matt Schaub scored on a quarterback draw with three seconds left to seal a 29-28 victory over the Miami Dolphins.
Not all the games were close and Philadelphia scored 23 points in the fourth quarter as they thrashed San Francisco 40-26, while Peyton Manning threw three touchdown passes as the Indianapolis Colts cruised to a 31-3 victory over the Baltimore Ravens.
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