The 22-year-old Texan, whose five wins this season included the Masters and US Open, fired a final round 69 for 271 and a four-shot win over Sweden's Henrik Stenson, New Zealand's Danny Lee and England's Justin Rose.
With the win - and Jason Day's 10th-place finish - Spieth will recapture the number one ranking Day had held for a week.
He also set a US PGA Tour record for earnings, the Tour Championship first prize of US$1.485 million (S$2.116 million) taking his total for the year to US$12,030,465 - not including the US$10 million bonus that came with his FedEx Cup playoff title.
Spieth started the day with a one-stroke lead over Stenson, and the Swede - who could also have seized the playoff bonus with a victory - tried to keep the pressure on.
Back to back bogeys from Spieth at the fifth and sixth saw Stenson pull level, but Spieth was just too good on the greens.
He poured in a 21-foot birdie putt at the eighth as Stenson bogeyed to restore his two-shot cushion.
He drained an 18-footer at the ninth, and bounced back from a bogey at 10 with a 47-foot birdie putt at the 11th.
The rest of the way Spieth found the clutch par putts when he needed them, as Stenson's race for the title turned into a battle to hang on to at least a share of second.
Stenson managed to do just that by rolling in a long birdie putt at the par-three 18th to cap a two-over 72.
That was good enough to join Lee and Rose in second place, Lee climbing up the leaderboard with a five-under 65 and Rose signing for a 66.