Flesch ended the event at 11-under-par 269 to become the first PGA Tour player to win on his birthday since David Edwards won the 1993 MCI Heritage Golf Classic in Hilton Head, S.C.
'I hit it so well, it would have been a shame not to win,' said Flesch, who earned $954,000 for the win. 'I'm thrilled to death. This is a ballstriker's course. It's not a power course.'
Stephen Ames fired the low round of the day as he posted a 6-under 64 to finish in third place at 9-under-par 271. He was joined there by Craig Perks, who posted a 68.
Flesch began the day at Colonial Country Club tied with Campbell and Brian Gay in first place. Campbell moved ahead of that duo with a birdie at the first. Flesch joined Campbell atop the leaderboard at minus-9 with a birdie at the third.
After a par-saving putt from 12 feet at the sixth, Flesch dropped a pitching- wedge within 8 feet at the next. He ran in that putt for solo first place.
Flesch, who won the HP Classic of New Orleans last year, ran off three straight two-putt pars. Campbell meanwhile drained a birdie at the ninth to tie Flesch at minus-10.
Flesch regained first place by himself when he two-putted for birdie on the long par-5 11th. Campbell did the same to tie Flesch at 11 under.
The would be the last tie however. Campbell was unable to get up-and-down for par at the 12th and slipped back to 10 under with his bogey.
Flesch got up-and-down for par on the 13th, and two-putted for par on the next two holes. The University of Kentucky alum knocked a 7-iron within 18 feet to setup birdie at the 16th.
He calmly rolled in the birdie putt to move two shots clear of Campbell. Flesch tripped to a bogey at he 17th when he knocked his second shot over the green and left his first chip short of the putting surface.
'I hit it really well on the back nine and made a couple of good saves out of the bunkers on 12 and 13, which were really big,' Flesch said. 'On 17, I just kind of got ahead of myself. I was so in between clubs, I couldn't have picked a worse yardage. I hit a poor shot and it rode the wind and I kind of maybe lost my focus for a minute.'
Flesch two-putted for par on the last and it was off to the scoring tent to watch Campbell finish up.
'I think I did that last year, as well. It was just one of those things,' said Flesch of the fact that he was the only player with four rounds in the 60s. 'Colonial is just a place that's good for me. Either way, I always love coming back here. I've been preaching all week how much I love the golf course and that if there was a good spot for me to win, it would be here.'
Campbell also struggled to a bogey at the 17th. He drove it in the trees, then punched his second shot into a greenside bunker. He knocked his third shot on the green, but was unable to make the par-saving putt.
The 2003 Tour Championship winner found the fairway off the 18th tee. Needing to hole his second shot to force a playoff, Campbell stuck a sand-wedge within four feet of the cup.
The birdie gave him solo second thanks to a 2-under 68, but was not enough to force a playoff.
'I felt good going into today and was playing well on the front nine,' Campbell said. 'I had some lip-out putts, but that's the way it goes. I hit a lot of bad shots on the back nine. I hit a good shot on the last hole trying to make it, but it was just a little short.'
Bo Van Pelt posted a 5-under 65 Sunday to climb into a share of fifth place at 6-under-par 274. He was joined there by Robert Gamez, Tim Petrovic and Skip Kendall.
Mark Brooks, John Senden and Jeff Maggert were one stroke further back at minus-5. Kenny Perry, the 2003 champion, closed with a 2-under 68 to share 12th place at 4-under-par 276. He was joined there by Loren Roberts.
Gay struggled to a 5-over 75 in the final round. He led a group of 12 players at 3-under-par 277.