Bickerton completed four rounds at 11-under-par 273 and earned $805,200 -- his largest career check and one of the top prizes on the European Tour. It was the 36-year-old Englishman's second tour victory.
'I've been out here a long time and it's nice to put some icing on the cake,' said Bickerton, who climbed to fifth on the tour money list and 10th on the European Tour Ryder Cup points list.
Harrington closed with a 5-under 66 to reach 10-under-par 274, claiming second place two weeks after finishing fifth at the U.S. Open.
Third-round leader Michael Campbell, the 2005 U.S. Open champion, sputtered in his final round, carding two bogeys and a double bogey at the 18th hole to finish with a 2-over 73 at Le Golf National's Albatross Course.
Campbell tied for third place with Marcus Fraser and Ian Poulter -- who both shot 69s -- at 8-under-par 276.
Bickerton has played 13 seasons on the European Tour, but it took him 12 seasons -- and 287 starts -- to claim his first title at the Abama Open de Canarias in October.
Career victory No. 2 came just 20 starts later and left Bickerton in a joking mood when asked what the title meant for the rest of the season.
'It means I'm a lot richer,' Bickerton said, laughing. 'This should make the year a lot more pleasing.'
Entering the round, Bickerton was one shot behind Campbell -- but with a birdie at the third and a Campbell bogey at No. 7, he held the lead around the turn at 10 under.
After both players birdied the 11th, Bickerton stuck his approach at the par-4 12th within a foot to set up another birdie and take a two-stroke advantage.
A 10-foot birdie putt at the 14th gave Bickerton a solid three-shot lead, but he ceded a shot at the 15th, where Campbell's bogey was still one stroke better than the leader's double bogey.
Bickerton's six at No. 15 was the result of him knocking his approach into the water guarding the green.
'It spun in the air and ballooned on me, so I had a lot of work to do after that,' Bickerton said.
Campbell gained a stroke with a birdie at the 16th, but found water and double bogeyed the 18th to hand Harrington second place alone.
Bickerton finished his round with three consecutive pars, including a scrambling four at the 17th where he saved himself with a chip to 7 feet after finding the rough twice.
The championship was sealed with a two-putt par from 35 feet on the 18th green. Bickerton left himself with a 2-foot knee-knocker to make the par.
'It was a little bit nerve-wracking coming down that last hole, which didn't make that last putt any easier,' said Bickerton. 'But I enjoyed it nonetheless.'
Harrington placed runner-up for the 22nd time in 10 years playing on the European Tour. His 66 on Sunday included seven birdies and two bogeys.
'I forgot how difficult taking second was,' said Harrington, a nine-time European Tour winner. 'But sometimes you have to be in the hunt before you win.'
Anders Hansen shot a 71 and finished in sixth place at 7-under-par 277, one shot ahead of Andrew Coltart, Richard Green and Peter O'Malley.
The oldest of the European continent Opens, this event was celebrating its 100th anniversary. Jean Van de Velde was the best among the French finishers, tying for 17th at minus-3 after a final-round 72.
France's Jean-Francois Remesy entered as the two-time defending champion. He shot a 73 on Sunday and tied for 40th place at plus-1.