The scoring at TPC Deere Run tends to be low, and Thursday proved to be no exception, with Thomas and Thompson edging ahead of Luke Guthrie (64) and Charles Howell III 64), with three-time champion Steve Stricker (65), Daniel Summerhays (65), Robert Garrigus (65) and Shawn Stefani (65) a further shot back.
World number two Spieth was not able to take advantage of the favourable conditions, and had to settle for a even-par round of 71 to sit eight shots off the pace.
Thomas' strong showing was particularly impressive in the context of his recovery from a nightmare end to the Greenbrier Classic last week. With a first PGA Tour title in sight, Thomas' putter went horribly cold as he dropped seven shots in the last 10 holes, including an eight at the par-four 16th to finish in a tie for 54th.
The American had no such trouble on Thursday, as he knocked in 10 birdies, including a 51-foot putt for a birdie two at the 16th.
Thompson joined his compatriot at the top of the leaderboard after registering seven birdies, an eagle and a lone bogey. An eagle-two at the par-four 14th was the highlight for Thompson.
Spieth, who will go in search of his third major title at the Open at St Andrews next week, admitted that he was a bit rusty on Thursday after taking a break last week.
The 21-year-old slumped to three bogeys in four holes from the eighth to the 11th as he struggled to get going. A birdie at the 13th after sinking a 32-foot putt looked to have sparked something when Spieth followed it up with another birdie at the 14th, but that run quickly ended when his tee shot at the 15th flew into the gallery.