The two-times Masters champion, who missed the cut last week at Chambers Bay by two strokes, made nine birdies and one bogey at TPC River Highlands in Cromwell, Connecticut, en route to an eight-under-par 62.
That gave Watson, at number five the highest-ranked player in the field, a two-stroke cushion over a group of five players that included 2011 PGA Championship winner Keegan Bradley and South Korean Noh Seung-yul.
Watson birdied the par-four 15th to take sole possession of the lead before falling back into a share of the lead after giving a stroke back at the par-three 16th. But he closed his round with consecutive birdies to take command.
At the par-four 18th, Watson's approach shot from 139 yards bounced three times on the green before hitting the flagstick and settling inches from the cup for a tap-in birdie.
The American is clearly comfortable with the layout having finished in the top five in three of his last five appearances at the Travelers, including his first PGA Tour title in 2010 when he triumphed on the second hole of a sudden-death playoff.
Bradley, who finished in a share of 27th place at the US Open, was two-under on the outward nine and capped his round with four birdies over a sizzling six-hole stretch that gave him a share of the early clubhouse lead until Watson took over.
Patrick Reed (67), who was the co-leader after two rounds at Chambers Bay last week, was five shots off the pace after mixing four birdies with a bogey.
Defending champion Kevin Streelman (69) was in a share of 76th place, seven shots back, after mixing five birdies with two bogeys and a double-bogey.
Original source: Watson shrugs off US Open flop