Scott, in his final tournament before he defends his green jacket at the April 10-13 Masters, took advantage of his morning tee time at the Bay Hill course in Orlando.
Wielding his long putter like a magic wand, the Australian mixed two eagles with seven birdies and a bogey to match his career low round on the PGA Tour.
He led Spaniard Gonzalo Fernandez-Castano by four strokes with half the field still on the course.
"I'm really thrilled with the start today," Scott, making his first Bay Hill start since 2009, told reporters. It's maybe a little surprising.
"I don't know where it came from but the putter certainly got hot today. Today was just one of those days where the hole was a like a bucket."
World number two Scott is regarded by many as the best driver in the game, but his short game proved just as good on Thursday as he pulled away from the field.
He drained putts from at least 20 feet on five occasions, including a 30-footer from off the green at the par-four 15th, where he threaded his ball between a couple of sprinkler heads.
Scott began his round at the 10th, and made a confidence-boosting start by sinking a 20-foot birdie right off the bat.
He got up-and-down from a greenside bunker at the par-five 12th to go two under, before picking up further birdies at the 14th and 15th holes.
An eagle at the par-five 16th, where he hit a mid-iron from 200 yards to 35 feet, took him to six under, while his lone bogey came at the par-four 18th, where he hit his tee shot left and also missed the green left with his second shot.
But that proved a minor hiccup, as he roared back with a birdie at the par-four third, followed by a 20-foot eagle at the par-five fourth.
Further birdies at the par-five sixth and par-four seventh took him to 10 under. He missed a good birdie chance at his penultimate hole, before ending his day with a long two-putt par to match the course record held by Andy Bean and his boyhood idol Greg Norman.
Scott is playing just his third tournament since mid-January. He has reduced his tournament schedule over the past couple of years in order to prepare for the majors in peace and quiet.
The 33-year-old is the top-ranked player at Bay Hill in the absence of defending champion Tiger Woods, who withdrew from the event earlier this week with a bad back.
Former Masters champion Bubba Watson withdrew from Bay Hill citing allergies following an opening-round 11-over-par 83 that included an 11 at the par-five sixth and a triple-bogey seven at the par-four 18th.
- Sports & Recreation
- Bay Hill