Mickelson made only one bogey and got hot with his irons on the back nine with back-to-back birdies inside 5 feet and a 3-wood from 287 yards that set up an eagle on the 17th hole, sending him to a 6-under 65 and a chance to win for the second straight week.
Harrington only made two pars on his first 10 holes, a round filled with brilliance and bogeys, until he finally settled down in the twilight hours off Sunset Boulevard to polish off a 68.
They were at 11-under 131, three shots clear of Charles Howell III, who shot 65.
"Anything in the 60s was really the goal today," said Harrington, playing the Nissan Open for the first time. "I knew going out there I would be a little erratic. I'm still making mental errors here and there, so I put up with that. And I made some birdies to counteract some of the bogeys, which was very nice."
Mickelson hasn't played Riviera since 2001, and he only added this tournament to his schedule at the last minute to test the newfound confidence in his driver. Two rounds, he hasn't found any flaws.
"I like the way I put the ball in play," Mickelson said. "It feels easy."
He reached all three par 5s in two, none more impressive than the 17th. Coming off his only bogey of the tournament, when he pulled his tee shot into a back bunker on the par-3 16th, Mickelson hit a bullet of a tee shot down the left side of the fairway some 310 yards. He followed that with a hard 3-wood that drew slightly and found the middle of the green, rolling to 15 feet.
"I was just trying to get down there by the green in two," Mickelson said. "I still wanted to be left so I would have a good angle to the green, and I just flushed it. It came off perfect."
It was another command performance, similar to last week at Pebble Beach when he won by five shots. He only missed four fairways, but none of them were off the fairway by much, and he never had a problem going after the flag. The only glitch was a few irons that he pulled, but it only cost him a bogey on the 16th.
Mickelson finished his round with an approach that sailed right of the green, but a flop shot landed softly and trickled 4 feet below the hole, allowing him to save par and go into another weekend in the final group. The next quiz comes on the weekend, for Mickelson has made the cut only five times in nine tries at the Nissan Open, and he has never finished in the top 10.
"It's a good start for two rounds," Mickelson said. "But one of the best players in the world, Padraig Harrington, is tied for the lead. The greens are going to be firm. It's going to be hard to get the ball close to the hole. It's going to be a challenge."
Harrington found himself scrambling from the start, three-putting for bogey on No. 10 when he missed a 4-foot putt. But every mistake was followed by birdies on par 3s and good wedge play.
Howell was in the first group off and matched Mickelson for the best score of the day, playing bogey-free for a 65 to finish at 134. Howell made four straight birdies around the turn, two of them par 5s.
Sergio Garcia chipped in for birdie on the 17th on his way to a 68 and was in the group at 135 that included David Howell (68) and Pat Perez (69). Ernie Els didn't hit a fairway on the back nine until the 18th hole, and missed birdie putts inside 12 feet on his final two holes for a 68 that left him at 5-under 137, along with Jim Furyk (70) and Rich Beem (68).
Mickelson and Harrington never saw each other being on different nines, but they finished up along the adjacent ninth and 18th fairways about 10 minutes apart. The only difference was the size of the gallery, most of them with Mickelson.
"I prefer playing with the noise,Harrington said of the third round. "It's a lot easier to play with a big gallery, a noisy gallery."
Charles Howell III hasn't won in five years, but he took another step toward ending that drought. He already has two runner-up finishes this year, at the Sony Open and Buick Invitational. Howell matched Mickelson with the best score of the second round, making four straight birdies around the turn.
"The best thing I can do is keep giving myself chances," Howell said.
Divots:@ Mickelson got a few tips on the greens earlier this week from Hall of Famer Amy Alcott, a member at Riviera. "I hope he listened to me," Alcott said with a laugh. ... George McNeill was the only player who didn't finish his round before darkness. He was at 1 under and faced a 40-foot birdie putt on the ninth hole, which he will play Saturday morning. The cut will be 1-over 143. ... Retief Goosen made a hole-in-one on the 16th. He shot a 70 and was at 141. Vijay Singh shot 71 and was at 139. ... Mickelson is flying between Riviera and his home in San Diego County, a commute that takes about an hour door-to-door. Twice this week, he has arrived home before his caddie, Jim Mackay, could get to his hotel room near the Los Angeles airport, about 20 miles away. "He's about 15 minutes away, but it's taking him 2 1/2 hours," Mickelson said.