Spieth, 20, won PGA Tour rookie-of-the-year honors for his 2013 season and he already has a runner-up finish to his credit this year at the Tournament of Champions.
He birdied half the holes on the Torrey Pines North Course Friday for a 9-under 63 that put him at 10-under 134 for 36 holes.
Spieth was paired with world No. 1 Tiger Woods for the first two rounds and bested Woods by nine shots.
The previous low 18-hole score on the tour for Spieth had been a 64 shot in the fourth round of last year's Tour Championship, where he wound up second behind Henrik Stenson. Spieth has finished fourth or better in five of his last 10 starts.
First-round leader Stewart Cink, seeking his first victory since winning the 2009 British Open, shot a 71 on the South Course and was alone in second at 135. The South Course is by far the more difficult of the two layouts used for this tournament and it is where those who made the cut will play during the final 36 holes.
The best round turned in on the South Course during the opening two days of the event was a 5-under 67 shot Friday by Nicolas Colsaerts, who was in third place at 136.
Billy Horschel and Marc Leisham tied for fourth at 137 while the group at 138 included Gary Woodland and Pat Perez.
Phil Mickelson survived the 36-hole cut at 2-under 142 after shooting a 73 on the South Course. Woods settled for a 71 on the North Course and wound up tied for 50th at 143