Rose secured the Order of Merit by reaching a three-way playoff at Valderrama, where the Englishman rolled in a 12-foot putt at the second extra hole to win the season-ending tournament over Simon Dyson and Soren Kjeldsen.
Rose rallied after blowing a four-shot lead with nine holes to play, finishing with a 3-over 74. Dyson shot a 70 and Kjeldsen had a 67. They tied at 1-under 283.
"On the 16th hole I actually looked like losing the Order of Merit as well as the tournament," Rose said. "I saw Graeme McDowell had made an albatross. Padraig (Harrington) was maybe going to even par up in front of me, Soren was 2 under. It looked like it was very much in the wrong direction."
Rose, however, quickly turned it around, shooting a 192-yard 7-iron to within 15 feet at the par-5 17th that allowed for a two-putt birdie.
"I'm not out there shaking like a leaf anymore. I'm out there calm, pretty collected," the 27-year-old Englishman said. "I feel like I'm in control."
By the time he was heading back out for the first playoff hole, Rose's name was already being engraved into the Harry Vardon trophy since the top-three finish meant he had overtaken Ernie Els to top the European Tour's money list.
"It's emotional. It was a hard day," Rose said. "It's been a long road to get here, but I feel great."
Rose overtook Els - who opted to play on the Asian Tour this weekend - and Harrington thanks to Valderrama's winning prize of $960,488. He topped the money list with $4,276,062 after 12 tournaments, the fewest played by any champion in the Tour's modern history.
"That's been the key for me, consistency," said Rose, who moved up to No. 7 in the world rankings and top of the Ryder Cup points list for Europe with his second victory of the year.
"That's why the win was so valuable today, I've had a lot of top-10 finishes and three seconds and I think that's what was missing from the year, a win."
Harrington, who won last year's Order of Merit title after finishing in a three-way tie for second at Valderrama, couldn't make birdie putts at Nos. 17 and 18 that would have gotten him into the playoff. The British Open champion shot 1-over 72 to finish two shots back in a tie for fourth with McDowell (68).
"I'm disappointed, I didn't putt well today," Harrington said. "I tried to hole that putt at No. 18 and put a little pressure on him."
Rose had a four-shot lead after sinking a birdie at No. 9, and was soon six ahead of Harrington.
But Rose's round began to unravel at the 11th. A double-bogey was followed by bogeys at Nos. 13 and 14.
McDowell holed his second shot at No. 17 for the albatross-2, while Kjeldsen birdied. Both players then bogeyed No. 18.
Kjeldsen, who had three birdies in his first five holes for the day's lowest score, watched from the clubhouse as Rose and Dyson missed par putts to send it to a playoff.
The last time the tournament went to a playoff, England's Ian Poulter beat Sergio Garcia of Spain in 2004.
Rose is the first Englishman to take the season-ending money title since Lee Westwood did in 2000. The trophy has been awarded annually since 1971.
Els, who took the Order of Merit in 2003 and 2004, finished with $3,624,407 and Harrington was third with $3,577,355.
Harrington, who led Rose by $948 coming in, cut the Englishman's advantage to three strokes by making a 10-foott birdie at the par-4 first.
Rose answered with a birdie on the par-5 fourth, and went up five shots when Harrington, playing one group ahead, couldn't make a 22-footer for par.