The 22-year-old American, who captured the US Open crown as well as a green jacket last year, matched the low first round by a defending champion with a six-under par 66 to own a two-stroke lead after 18 holes.
Spieth is trying to join Jack Nicklaus, Tiger Woods and Nick Faldo as the only players to win the Masters two years in a row.
The Texan teed off in the second round at Augusta National with no rival nearer than three strokes, including English playing partner Paul Casey, who opened with a par to fall four back.
Spain's Sergio Garcia, seeking his first major title at age 36, sandwiched birdies at two and three between bogeys at the first and fourth but then put his approach to three feet at the par-5 eighth and made the birdie putt to reach four-under, three back of Spieth in second.
Four-time major winner Rory McIlroy and Irishman Shane Lowry were among those falling back as most challengers stumbled in failed bids to catch Spieth.
McIlroy, trying to complete a career Grand Slam with a Masters title, was on one-under.
He had back-to-back birdies at the second and third, but stumbled to a double bogey at the par-3 fourth, where he found a bunker off the tee and three-putted from 20 feet, and a bogey at the fifth, taking two shots to escape greenside rough.
Lowry began bogey-bogey to fall five adrift.
World number one Jason Day was fighting back issues, laying on his back and raising his leg on the second fairway and stretching to relieve the trouble on the third tee.
But after a bogey-birdie start, Day found his form and birdied the fifth and par-5 eighth only to bogey 11 and fall to one-under.
Day will lose the top spot to second-ranked Spieth if the US star wins the title again and the Aussie finishes beyond the top five.
England's Justin Rose, the 2013 US Open champion who opened on 69, was set to start later in the penultimate group.
American Scott Piercy birdied the second and third holes, but a bogey at the seventh dropped him to three-under while Dane Soren Kjeldsen birdied the second only to bogey to the par-3 fourth and the ninth to fall to two-under.
South Korean-born New Zealander Danny Lee, who opened on 68 in a share of second with Lowry, birdied the par-5 second from seven feet but followed with a double-bogey at three -- reaching the green in two but missing a four-foot birdie putt and a six-foot par putt.
He made a 13-foot birdie putt at the fifth but a bogey at the par-3 12th left him on three-under.
No Kiwi has won a US event since Michael Campbell captured the 2005 US Open.
Ernie Els, the 46-year-old South African who fired the worst score ever recorded on the first hole with a nine in round one, managed a double-bogey six in the second round.
The four-time major champion sent his approach way left onto the adjacent ninth hole, punched the ball onto the green 47 feet shy of the cup.
He missed his long par putt, then knocked a two-footer past the hole before sinking a comeback four-footer.
Eight-time major champion Tom Watson could be playing the final round of his legendary career Friday.
The 66-year-old American, who opened on 74, teed off in the early afternoon hoping to become the oldest player to make the cut in Masters history in his final competitive event.
Among those struggling to make the cut were two-time Masters champion Bubba Watson, fellow American Rickie Fowler and South Africans Els and Charl Schwartzel. – AFP
Original source: Spieth off to a flyer