Woods, who led the standings for the PGA Tour Play-Offs going into the final counting event in Atlanta, bagged the $10m winner's cheque ahead of Mickelson, whose third win of the season helped him jump from 36th on the FedEx Cup standings to second.
Steve Stricker finished third, with Jim Furyk fourth and Sean O'Hair fifth. Padraig Harrington was the best-placed non-American in seventh.
"To win the FedEx Cup and to be as consistent as I have been all year is something that I'm very proud of," said Woods. "There were so many unknowns at the beginning of the season, and I certainly wouldn't have expected going into my first event to end up where I'm at right now."
Mickelson, meantime, commented: "It really feels great to have won. It's been a frustrating go the last few months and so to be able to come out and get somewhat in contention on a Sunday, four back, and then to be able to put together this round feels terrific.
"This wasn't a banner year but this certainly makes it a better year than it was."
World No.1 Tiger Woods has won his second FedEx Cup after coming runner-up to Phil Mickelson in the season-ending Tour Championship.