With the FedExCup playoff title and a bonus jackpot of $10 million also on the line at East Lake Golf Club, Stenson birdied the par-four seventh to reach the turn in one-under 34, 12 under for the tournament.
Rookie sensation Jordan Spieth and fellow Americans Steve Stricker and Dustin Johnson were tied for second in the PGA Tour's season-ending event.
The 20-year-old Spieth had completed 12 holes while Stricker and Johnson each had nine still to play.
Four strokes in front of the chasing pack overnight, Stenson had his lead trimmed to three when playing partner Johnson sank a slick, 15-foot birdie putt at the par-four third on a hot, muggy afternoon at East Lake.
While the Swede parred the first five holes, Johnson bogeyed the par-four fifth after finding the right rough off the tee to slip back to four behind.
Stenson appeared to be very relaxed and, as he stood on the tee at the par-three sixth, he playfully stroked the furry microphone cover held by one of the television crew.
The Swede struck a good tee shot there to par the hole, then watched as his lead increased to five, Johnson running up a bogey after chipping from just off the green to eight feet and missing the par putt.
Though Spieth closed in with three successive birdies from the seventh, Stenson struck a superb approach to three feet at the seventh to pick up his first shot of the day.
The Swede then parred the next two holes to hold a commanding five-stroke advantage heading into the back nine.
FedExCup points leader Tiger Woods, who was a distant 14 strokes off the pace overnight, ending his 2013 PGA Tour campaign with a three-under 67.
Seeking his sixth victory of the year, Woods struggled with his ball-striking from the opening round at East Lake but posted his best score of the week with a mix of five birdies and two bogeys to finish at level-par 280.