Though not quite matching the high standard of play he produced over the first two days at the TPC Summerlin, the American finished strongly with four birdies in the last seven holes to card a four-under-par 67.
That left Simpson at 19-under 194 in the second event of the US Tour's 2013-14 season, with 26-year-old rookie Chesson Hadley alone in second place after shooting a 67.
Ryder Cup player Jeff Overton (68) was a further stroke back at 14 under, one ahead of fellow American Jason Bohn (69).
Simpson, however, commanded the spotlight as he remained atop the leaderboard on another ideal day for low scoring in the high Nevada desert where there was barely a breath of wind.
Four ahead of the chasing pack overnight, Simpson briefly dropped back into a tie for the lead with Bohn at 14 under after running up a three-putt bogey at the par-four third.
However, he immediately recovered with birdies at the fourth and fifth to move two strokes clear, then parred the next four holes to reach the turn with a three-shot advantage at 16 under.
Simpson made another misstep at the par-four 11th, finding the left rough off the tee and failing to reach the green in two on the way to a bogey for his lead to be cut to two.
Once again, though, he quickly rebounded with consecutive birdies, sinking a 12-footer at the par-four 12th and a 25-footer at the par-five 13th to regain a four-stroke cushion.
Simpson picked up further shots at the driveable par-four 15th, where he two-putted from the fringe, and at the par-five 16th, where he narrowly missed an eagle putt from 32 feet before tapping in for birdie.
Simpson safely parred the last two holes to remain four strokes clear in pursuit of his first USTour win since the 2012 US Open.
Sean O'Hair fired a best-of-the-day 63 to finish at 12-under 201, level with five others including fellow American William McGirt (64), Scotland's Russell Knox (69) and Japan's Ryo Ishikawa (68).