He stands at 18-under-par 198 and is two in front of Scott Verplank, who shared the overnight lead with Rose.
This is the only five-round tournament on the PGA TOUR schedule. The format sees each player grouped with amateurs over the first four rounds before the cut is made.
The golfers compete on four courses -- Bermuda Dunes Country Club, the Arnold Palmer Private Course at PGA West, La Quinta Country Club and The Classic Club, which will host the final round on Sunday.
Rose carded his 66 at the Palmer Course at PGA West. Verplank shot a 4-under 68 at Bermuda Dunes to complete 54 holes at minus-16.
First-round leader Robert Allenby (70/CC), Lucas Glover (66/BD) and John Rollins (69/LQ) are knotted in third place at 13-under-par 203. Charley Hoffman shot a 4-under 68 at the Palmer Course and is alone in sixth place at minus-12.
The conditions, as they have been all week, were trying on Friday. The temperatures dropped considerably and the wind gusted over 20 miles per hour.
Rose was not immune from the conditions either, but was out in one of the later rounds on Friday. He teed off on the 10th hole at the Palmer Course and wasted little time in breaking into red figures.
At the par-5 11th, Rose hit a fairway-wood to 6 feet and drained the putt for eagle. He added back-to-back birdies from the 13th, but dropped a shot at No. 16.
Rose, an Englishman who tied for fourth as an amateur at the 1998 British Open, two-putted for birdie at the par-5 18th hole. He kept the strong play going with an 8-foot birdie putt at the first to keep the pace with Verplank at 17-under par.
When Verplank tallied a late bogey in his round, Rose was alone in the lead. Rose had a chance to pad the lead, but missed a 4-foot birdie try at the second.
Rose holed a pair of five-foot par saves at four and five, then took a two-shot lead with a birdie at the par-5 sixth. He parred out for the 54-hole lead as he is in search of his first win on the PGA TOUR.
Like everyone in the field, Rose was talking about the impact of the weather.
'The conditions were surprising today,' acknowledged Rose. 'Luckily I managed to keep my end of the bargain with the scoring which is good. I played very, very well today because there was some demanding par-fours out there.'
Verplank, who tied for second last year behind Chad Campbell last year, flew out of the gate on Friday with a birdie at the first hole. He added a 15-foot birdie putt at the sixth to move to 14 under par for the championship.
At the par-five eighth, Verplank reached the green in two and came up short on his 35-foot eagle try. He tapped in a short birdie putt, then sank a 4-footer for birdie at the ninth.
Verplank, twice an American Ryder Cupper, birdied the 14th to get minus-17, but trouble loomed. At the par-4 16th, Verplank's approach ran through the green to the back fringe. He chipped to 6 feet, but missed the par putt. Verplank parred his final two, including a 7-foot par save at 17 and a missed 6-footer for birdie at the last.
Verplank was just happy to complete his round in such trying conditions.
'When I left home and came out here, I thought I was headed to Palm Springs, but I think I ended up in Seattle or something,' joked Verplank. 'You like to leave the golf course thinking you got everything out of your round and I didn't today, but with conditions tough like today, I'm just happy to be done.'
Reigning Masters champion Phil Mickelson, making his first appearance since the Ryder Cup in September, is still floundering. He recorded a birdie and an eagle in his first four holes, but only played even-par the rest of the way.
Mickelson shot a 3-under 69 at the Classic Club and is part of a large group tied for 41st place at seven-under-par 209.
Charles Warren (66/LQ), John Senden (68/BD), Joe Durant (69/LQ), Matt Kuchar (71/PW), Dean Wilson (67/PW) and Heath Slocum (69/BD) are tied for seventh place at minus-11.
Campbell shot a 2-under 70 at the Palmer Course on Friday, but is danger of missing the cut. He stands in a tie for 83rd place at 2-under-par 214.