Scott carded two eagles, seven birdies and one bogey to set a daunting clubhouse target of 10 under par, matching the course record shared by Andy Bean (1981) and fellow Australian Greg Norman (1984).
"Obviously I'm really thrilled with the start," said Scott, who is closing in on Tiger Woods at the top of the world rankings ahead of his US Masters defence in three weeks' time.
"It's maybe a little surprising. I don't know where it came from, but the putter certainly got hot."
Scott is making his first appearance at Bay Hill since 2009. He missed the cut in his last two starts and his only top-10 finish in six previous appearances came in 2004, when he tied for third.
"I just had a few frustrating years here and left it off the schedule," Scott told reporters after his round. "Coming back fresh was obviously a good thing.
"But I like the changes they've made since the time I have not been here. And today was just one of those days where the hole was a bit like a bucket."
The reigning Masters champion started on the 10th and birdied his opening hole before picking up another shot on the par-five 12th after getting up and down from a greenside bunker.
Scott then holed from 25ft on the 14th and from a similar distance off the green on the next, before continuing his hot putting steak by making an eagle from 35ft on the par-five 16th.
His solitary bogey came from an errant approach to the 18th, but the 33-year-old bounced back quickly with a birdie from close range on the third and another eagle from 20ft on the fourth.
Further birdies on the sixth and seventh meant matching front and back nines of 31 and left Scott four ahead of Spain's Gonzalo Fernandez-Castano, who also covered the back nine in 31 to return a 66.
England's Paul Casey was a shot further back on five under alongside American duo Morgan Hoffmann and Brandt Snedeker, while US Open champion Justin Rose and WGC-Cadillac Championship winner Patrick Reed - playing alongside Scott - shot 71 and 69 respectively.
Scott's predecessor as Masters champion, Bubba Watson, withdrew after an opening 83 - which contained an 11 on the par-five sixth - citing allergy problems.
Scott cannot overhaul the absent Woods - the defending champion pulled out on Tuesday with on-going back problems - with a victory on Sunday, but would claim top spot before his Masters defence if both players did not play again before the year's first major at Augusta.
Page 2: 19:52
English amateur Matthew Fitzpatrick returned a highly creditable 71, the 19-year-old from Sheffield carding three birdies and two bogeys.
"I felt quite composed, I didn't get down or get too upbeat," said Fitzpatrick, who claimed the silver medal as leading amateur in the Open Championship at Muirfield last year and then won the US Amateur title at Brookline.
That victory means Fitzpatrick has exemptions into three of the four majors in 2014 - the Masters, US Open and Open - as long as he remains an amateur. In January, he withdrew from Northwestern University to pursue a full-time amateur golf career.