Patten caught two scoring passes, including the longest pass play for a touchdown in New England history, threw for a score and also reached the end zone on a 29-yard run as the Patriots (3-3) rolled over the Colts (2-3) for the second time this season.
"It's good to come away from Indianapolis with a win," Patriots coach Bill Belichick said. "It's been awhile since we've been able to do that. We came ready to play today."
The 5-10, 190-pound Patten is the first player since Walter Payton in 1979 to pass, rush and catch a touchdown pass in the same game.
"It was one of those days where everything was clicking," Patten said. "Every time I touched the ball, I was able to make something happen. That's what I pride myself on. I think I'm able to do that every time I go on the field and today I made it happen."
Entering the game, Patten had just four receiving touchdowns. Originally signed by the New York Giants as an undrafted free agent out of Western Carolina in March 1997, he caught two touchdowns as a rookie and one the following season.
After totaling just nine receptions in 1999, Patten was waived by the Giants and picked up by the Cleveland Browns. He caught 38 passes, including one for a score, last season while playing in 14 games and starting 11.
On Sunday, Patten hauled in four passes for a career-best 117 yards, four more than his total against Baltimore last year. He rushed only once, but scored on that carry one play after Leonard Myers returned a blocked field goal 35 yards to the Indianapolis 29.
The Patriots, who share second place in the AFC East, handed San Diego its first loss of the season a week ago.
"It was a good day," Patten said. "Things were just clicking out there. I really can't take all the credit."
Mike Vanderjagt brought the Colts within 7-3 by booting a 43-yard field goal a little less than five minutes after Patten's rushing touchdown, but the Patriots, took control with a three-touchdown explosion.
"We didn't move the ball offensively," Indianapolis coach Jim Mora said. "Defensively, we couldn't stop them consistently. The three big plays in the first half hurt us. One-play drives for touchdowns, that makes it tough."
All three scores came within a 7:44 span of the second quarter and the onslaught began when Tom Brady, making his fourth straight start in place of the injured Drew Bledsoe, hit a streaking Patten for a 91-yard touchdown.
The Patriots are 3-1 with Brady at the helm. The second-year Michigan product on Sunday completed 16 of 20 for 202 yards and three touchdowns while his counterpart, All-Pro Peyton Manning, was 22 of 34 for 335 yards and a score.
"It was a great overall team win for us," Brady said. "We came in and knew we were going to get their best shot. Just a great win for the Patriots. Now we're back to .500."
New England resorted to some trickery on its next possession as Patten took the ball from Brady and proceeded to loft a 60-yard touchdown pass to Troy Brown, who totaled 120 yards on eight receptions.
"We started to run that play in practice but with Troy throwing the pass to David," Belichick said. "Patten caught it and whipped the ball back about 30 yards past everyone, letting us know he could throw the pass as well as catch it. A few days later we had some tryouts, and out of those tryouts we decided to switch those two."
Brown's touchdown reception made it 21-3. After a fumble by Edgerrin James, Brady capped a six-play drive by connecting with Jermaine Wiggins for a two-yard touchdown with just 1:15 to play in the opening half.
James rushed 30 times for 143 yards as the Colts outgained the Patriots, 484-385.
"You never like losing," said Mora. "It's not good when you're losing. Certainly there are more negatives than positives. You can always find some positives. We did some good things, but certainly you didn't do enough when you get beat like this."
A 42-yard field goal by Vanderjagt with nine seconds to play before the break made it 28-6 and Manning hit Marvin Harrison for a two-yard score early in the fourth quarter. After the two-point conversion, Indianapolis trailed, 28-14.
However, the Colts were only able to manage another Vanderjagt field goal the rest of the way and Patten capped his remarkable day by hauling in a six-yard touchdown pass from Brady in the first minute of the final quarter.
"A combination of things (went wrong today)," said Manning. "We got beat and we don't have any time to think about it or dwell on it. We have a game on Thursday. We will come in tomorrow and work and try and get a win against the (Kansas City) Chiefs."