Vijay Singh shot a 6-under 65 to finish two shots off the lead along with Cliff Kresge.
Tiger Woods was not as fortunate despite a promising start. The top player in the world eagled the par-5 second but found trouble with a bogey at the very next hole.
Woods' problems continued on the back nine where he had a rocky ride coming home with three birdies and three bogeys to finish in a group at 1-under-par 71.
'I played pretty good,' said Woods. 'I just made absolutely nothing. The worst part is that I hit decent putts that just didn't go in.'
Rose, who has established himself as a rising start overseas, has been waiting to make an impact on the PGA Tour.
'I think you look a lot at the majors and the world championships as your sort of targets and what you want to peak for,' said Rose. 'So I think for a European, and being top-50 in the world, it's great to come over and get some match practice before the big ones. I mean, they are all big over here.'
The young Englishman wasted little time Friday at the TPC of Boston with a birdie at the first after his sand-wedge approach landed within two feet of the cup.
The 23-year-old kept knocking it close to the pin throughout the front nine. He was left with a two-foot putt for a birdie at the fourth and followed that up with a birdie at the fifth after his second shot stopped three feet from the cup.
Rose found a bunker at the par-5 seventh but hit out to set up another short birdie attempt.
'I was delighted,' said Rose. 'I got off to a fantastic start early on. I stiffed it on one and then stiffed it on four, five and seven.'
At the par-3 eighth, Rose's tee shot landed 20 feet from the cup but he calmly drained the putt for his fifth birdie of the day.
He missed a short birdie try at the ninth and got up and down to save par at the 11th but Rose's next birdie wouldn't come until the penultimate hole.
Rose hit an 8-iron to three feet for a birdie at the 17th and left himself with 14 feet for an eagle at the par-5 last. Rose ran home the putt to secure the first-round lead.
'I think it was just over the last two weeks,' said Rose. 'I just felt like everything sort of gelled together, like it all just clicked into place. Today I was a lot more aggressive through the ball. I think that mindset helped the swing just piece together.'
Kresge started well with four birdies on the front nine but stumbled with a bogey at the 10th.
He recovered with a 12-foot birdie at the 12th and hit a 3-iron that rolled within two feet of the hole for a tap-in birdie at the 14th.
Kresge added a birdie at the last for a round of 65.
'The course is very appealing to my eye and it sets up good for me,' said Kresge. 'If you hit good shots and you make putts you can be rewarded.'
Tim Petrovic, Brent Schwarzrock, Pat Bates, Steve Flesch, Arron Oberholser and Garrett Willis finished three shots off the lead at 5-under-par 66.
Darren Clarke, who won the WGC-NEC Invitational last week, was one shot further back at 4-under-par 68. Clarke was joined by Brian Henninger, Phillip Price, Tim Herron, Heath Slocum, Rocco Mediate and K.J. Choi in a tie for 10th.