The three-time major winner from Ireland opened with a 4-under par 68 and earned a share of the early lead with Florida's Billy Horschel at the Texas Open.
Harrington overcame the chilly temperatures and steady wind to go as low as 5 under before finishing with a bogey on No. 18. The former British Open and PGA Championship winner began his day with four layers of clothing in an attempt to stay warm as the Texas winds whipped in from the north.
"Last week back in Ireland, it was snowing, and I didn't feel as cold," Harrington said.
Rory McIlroy, who entered the tournament last week as a final opportunity to prep for next week's Masters, opened with an even-par 72. He was tied for 36th as the morning rounds finished up and the afternoon wave began.
The former world No. 1 was 2 under early in his round, which began on No. 10 on the difficult 7,435-yard layout.
However, McIlroy found the water on the par-5 18th when his approach came up short — beginning a stretch of three straight bogeys. He was 1 under entering his final hole of the round, No. 9, and missed a 7-foot par putt to fall back to even.
The up-and-down round was hardly what McIlroy, who has just one top 10 finish this year, envisioned when he added the tournament to his schedule.
"More mental than anything else," McIlroy said. "It's just about limiting those mistakes. It's definitely more mental mistakes than physical."
While McIlroy struggled, Horschel continued to show the form that led to a second-place finish at last week's Houston Open. Horschel jumped from 60th to 24th on the money list following last week's performance, and he tied Harrington on Thursday with a final-hole birdie on No. 9.
Horschel had six birdies, including a stretch of four in five holes midway through the round, and he did so despite hitting only 7 of 14 fairways. He and Harrington had just 25 putts each, while McIlroy needed 31.
Horschel has made the cut in each of his nine starts this year on the PGA Tour, a streak he hopes to extend on Friday.
"All in all, it's a good day," Horschel said. "I could hit the ball a little bit better, but I did a good job of managing it and making a couple putts."
Ottawa's Brad Fritsch finished his round at 2-under 70.
Jason Gore and Brian Davis finished a shot off the early leaders, posting 69s before stronger winds and warmer temperatures were expected to take hold in the afternoon.
Former Texas standout Jordan Spieth, playing on a special temporary membership, was 4 under with two holes remaining. The 19-year-old, however, landed near a cactus on his tee shot on No. 8 and took a triple-bogey 8 on the par 5.
Spieth finished with a 1-under 71, good for a tie for 18th with the round ongoing.