After back-to-back nine-under-par rounds of 63 in his first two rounds, the 23-year-old Texan started his third round in equally good touch and was seven under through 13.
Starting at the 10th hole of the PGA West resort's Nicklaus course, Reed had three birdies over his first five holes and then eagled the par-five 16th to surge well clear.
He picked up further shots at the first and fourth and was 25 under for the tournament with five holes left of round three.
Australian Matt Jones and American Brendon Todd were a distant second, the former six under for the day through 15 at La Quinta despite a double-bogey five at the par-three third.
Todd was taking things at a steadier pace and had 11 pars in his first 12 holes at La Quinta, his only deviation a birdie on 17.
Bill Haas and Justin Leonard were a further shot back, Haas three under for the day through 12 and Leonard five under after eight holes, but there looked to be no catching Reed as the third round drew to a close.