He posted a 12-under 130 halfway total, with Brendon de Jonge of Zimbabwe (68) the closest pursuer on nine-under.
Australian Jason Day, who has won three times in his last four events, including the PGA Championship, sat six shots back in a tie for 10th after successive 68s.
Masters and U.S. Open champion Spieth missed his second straight cut with a 73 for his fourth above-par round in a row.
It is the first time in his pro career that the 22-year-old Spieth has missed successive cuts.
With the PGA Tour taking a one-week break before the third event of the FedExCup playoffs, the BMW Championship near Chicago, the world number two plans to forget about golf for a few days before getting back to work.
“I’m going to take some time away, probably it’s going to be good for me to take four days and not touch a club,” he told reporters, largely blaming his putting for the six-over 148 total.
“I don’t feel it’s far off, even though my scores have been far off. It’s almost been like a bad dream, like I have to wake up and get the putts to go in again.”
Hoffman, a three-time PGA Tour winner who was on the leaderboard for a long time at the Masters this year before finishing equal ninth, started well with eight birdies on his opening 14 holes, including a near hole-in-one on the par-three 11th, his second hole.
“This is one of those courses that when you get up on the tees it sets up well visually for me,” American Hoffman said. “I also tend to make a few more putts on these greens.
“I’m in a nice position after two days, but obviously we have a lot of golf left.”
Northern Irishman Rory McIlroy was among those with a lot of ground to make up after the world number one shot 74 to fall 14 strokes behind.
(Reporting by Tim Wharnsby in Toronto. Editing by Andrew Both)
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