American Keegan Bradley was the pacesetter in Delaware, matching a career low with a 29 on the front nine, and finished with a seven-under 64.
With world No.2 Cameron Smith sidelined with a hip injury, Scott was the best performer of the four Australians with Marc Leishman tied for 13th at three three-under, Cam Davis a further stroke back while Lucas Herbert is one-under.
Scott started the post-season at No.77 and tied for fifth in the Fedex Cup playoff opener last week just to make it to the second stage.
Now at No.45 his eye is now firmly on making the US PGA's prestigious and lucrative season-ending Tour Championship in Atlanta, where the elite 30-man field at East Lake pocket a minimum $US500,000 ($A710,000).
The winner of the Tour Championship this year will collect a cheque for $US18 million ($A26m).
Paired with Bradley, they put on a show, combining for 15 birdies.
"He played beautifully today, and I was really just trying to follow his lead," Scott said.
"He kind of had everything going the way he wanted, and most of the time he was teeing off first and I was just trying to follow."
The 42-year-old Australian last tasted victory in 2020 but said he drew confidence from his showing at last week's St Jude Classic.
"I think more than anything out of Memphis I got some confidence out of having a result with maybe not my best stuff all four days," Scott said.
"It is a nice feeling walking on to any golf course when the confidence is a bit higher, and I certainly felt a sense of ease with that today.
"I've always prided myself on trying to win tournaments and managed to do that throughout my career, and it's been a while, and I'd love to get back there later this week, but we've got a bit of work to do."
Bradley is at No.44 in the FedEx Cup and likely needs a top 10 - he hasn't had one since the US Open to qualify.
"My plan is I'm going to go home and see my kids no matter what on Sunday night," Bradley said.
"I'd love to go to Atlanta. That's everyone's goal to start the year."
PGA champion Justin Thomas put a different putter in the bag and responded with a 66 to leave him in the group with former British Open champion Shane Lowry and Harold Varner III.
Xander Schauffele and Collin Morikawa led a group at 67.
Rory McIlroy was the only player from the afternoon who looked to challenge Bradley, and he was doing just that at six under with four holes to play.
But he ran into trouble on the par-3 15th when he tried to hit a soft cut with a five-iron and put his tee shot into the water.
He took three putts from just short of the green, missing a three-footer, and made triple bogey.
McIlroy was in the group at 68 that included Leishman, Jordan Spieth, world No.1 Scottie Scheffler and Patrick Cantlay, who won the BMW Championship last year on his way to capturing the FedEx Cup.