The Venezuelan had a two-shot advantage over a trio of major champions in Ernie Els, Zach Johnson and Lucas Glover, along with Canadian Ben Silverman.
Yet the big talking point in the lead-up to the first round was the absence of most of the game's biggest names.
Only three among the top 20 in the world rankings are present -- Justin Thomas, Brooks Koepka and Rickie Fowler -- making it the weakest field in more than a decade.
Tiger Woods, Dustin Johnson and Rory McIlroy are among those sitting out the event, even though they all live locally.
A number of big events both before and after the Honda Classic has left the longest title sponsor on the PGA Tour facing a problem not of its making.
Honda, which began sponsoring the tournament in 1982, comes directly after the WGC-Mexico Championship and only two weeks ahead of the Players Championship, a run that is too much golf for many on the tour.
The Players, the most prestigious event outside the four majors, has switched from May to March, while the PGA Championship has moved from August to May.
The tour season will finish in late August instead of late September.
The scheduling was of little concern to Vegas who notched six birdies in benign morning conditions on Thursday.
"I was able to drive... really well today, hit my irons incredibly well," said 34-year-old Vegas, who is ranked 131st in the world.
"I only missed three greens and of those I left two within 15 feet of the hole."
Veteran Els compiled six birdies for a share of second place with a round marred only by a double-bogey at the par-three 15th, where his eight-iron came up short and found the water.
The four-times major champion, now ranked 398th in the twilight of his career at age 49, said he enjoyed playing on a course with firm greens.
"They are not very receptive, even this morning, so going to get even firmer but I like that," he said.
"It means you've got to hit it on the fairways. (The ball is) not going to stop out of the rough so I'm trying to hit fairways and then you've got to hit it properly to stay on the greens."
Koepka and Fowler also started well, carding three-under 67, while defending champion Thomas shot 68.
German Alex Cejka was disqualified during his round for using greens reading material that did not fit the new scale.
(Reporting by Andrew Both in Cary, North Carolina; Editing by Toby Davis)
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