Seeking his fourth straight win at this event and his sixth overall, Woods fired a 7-under 65 on the Torrey Pines North Course for a 36-hole total of 12-under 132.
The world's top-ranked player has not bogeyed a hole this week.
Woods' closest competitor is Kevin Streelman, who is playing in only his seventh PGA Tour event. Streelman made it successfully through this year's qualifying tournament and he barely avoided disqualification this week when he showed up for his Thursday tee time with only minutes to spare.
Streelman shot a 69 Friday for a 136 total and will be paired with Woods for Saturday's third round.
"I don't know if it's really set in yet," Streelman said. "I'm really looking forward to it, to be honest. It's still just me and the golf course."
Phil Mickelson, making his first appearance of the season, was tied for 40th at 143.