Woods shot a 4-under 68 and is two shots clear of the field at 17-under-par 199.
Daniel Chopra (68) and 2002 PGA Champion Rich Beem (69) are knotted in second place at minus-15. David Toms posted a 2-under 70 on Saturday and is tied for fourth with overnight co-leader Camilo Villegas.
Last year, Woods trailed Mickelson by two in the final round, but overcame the deficit to hoist the trophy. On Saturday, they were the final pairing and were near the top of the leaderboard throughout most of the round. It wasn't until a late surge by Woods, coupled with some mistakes by Mickelson, that separated the two.
Mickelson, who shared the second-round lead with Woods, Villegas and Scott Verplank, found the water with his second at the final hole. He only managed an even-par 72 and shares sixth place with Tag Ridings (66) and Dean Wilson (69). The trio finished 54 holes at 13-under-par 203.
Woods broke out early with back-to-back birdies at one and two. When he tapped in a short birdie putt at the par-5 eighth, Woods owned a two-shot lead at minus-16.
Things fell apart quickly for the reigning Masters and British Open champion. He hit a terrible tee shot at the par-3 eighth and watched the ball splash in the lake. Woods re-teed it up and knocked his third to 15 feet. He missed the par putt, dropping back into a tie for the lead at 14 under par.
Woods parred the next three to stay near the top of the leaderboard. He turned it on starting at 13 when his 6-iron tee shot stopped three feet from the hole. Woods converted the birdie putt, then rolled in a 10-footer for birdie at 14. That putt allowed Woods to reclaim the lead at 16 under par.
Woods attempted to put some distance between himself and the field. He hit an 8-iron to 6 feet to set up his third birdie in a row. The No. 1 player in the world was 17 under par, but he could not shake the tour rookie.
Villegas came up short with his approach at the par-5 10th, but chipped to 5 feet to set up birdie. He sank a 16-foot birdie putt at 11 to get to 15 under par.
At the 14th, Villegas hit a spectacular approach inside 4 feet, but missed the birdie try. He atoned for the miscue at the par-3 15th when his 8-iron tee shot stopped inside 2 feet. Villegas holed that to match Woods at 16 under.
When Woods went past Villegas on the leaderboard with his birdie at 15, Villegas made a pair of routine pars at 16 and 17. The University of Florida product found serious trouble off the 18th tee.
Villegas drove never threatened the short grass and landed behind a huge tree. He was forced to punch out into the first fairway, then took a line of site drop as a tent was in his view. Villegas knocked his third to 28 feet, but his par putt came up almost five feet short. He missed the bogey putt and walked off the famed closing hole at Doral with a double bogey.
Woods' drive at 18 landed near the same tree Villegas found right before him. Woods was given relief because his feet were on the cart path and after several drops where the ball moved closer to the hole, he was allowed to place it, giving him a spectacular lie in the right rough.
He knocked his second to the right fringe, 27 feet from the stick. Woods chipped his birdie effort and came up a foot short. He tapped in for par to solidify his two-shot lead.
Davis Love III shot a 5-under 67 and is alone in ninth place at minus-12.
Verplank struggled to a 2-over 74 and shares 10th place with Fredrik Jacobson (68), Chad Campbell (71), Lucas Glover (71) and Zach Johnson (71). The group is knotted at 11-under-par 205.