Brown has banked on his likeability in the race, but he was aggressive throughout the debate, rarely missing a chance to attack his opponent.
The two sparred on jobs taxes, women's issues, global warming, and foreign policy during the wide-ranging, hour-long debate.
Some of the sharpest barbs came during a discussion of women's issues, which have been a recent focus of the race.
"I've been fighting for women's rights since I was 6 years old," said Brown, citing his troubled childhood. "I'm a moderate pro-choice Republican, I always have been."
Warren brought up Brown's vote against the confirmation of Elena Kagan for the U.S. Supreme Court, against equal pay for equal work, and for the Blunt amendment.
"You should stop scaring women, professor," said Brown at one point.
"Women need someone they can depend on, not some of the time, but all of the time," Warren said.
Brown repeatedly emphasized his bipartisanship, as he frequently does. "I was recently named by Washingtonian magazine as the least partisan senator," he said at one point. And Warren tied Brown to the national Republicans -- but in relatively small doses.
President Obama is expected to win Massachusetts by a huge margin in the presidential race, and she emphasized her support for him -- though didn't overtly say that Brown supports Mitt Romney.
"I'm still working to have President Obama be the commander in chief -- not Mitt Romney," she said during the foreign policy discussion. She made variations on the comment several times in the course of a few minutes, but let it hang rather than tying her opponent directly to Romney.
And only at the end of the debate did she link a vote for Brown to a vote for a Republican majority. After a question on global warming, Warren said that Brown had been asking for money, saying that he needs to be reelected so that Republicans can win the Senate majority. She invoked the idea of Oklahoma Sen. Jim Inhofe -- a Republican who thinks global warming is a hoax -- overseeing the EPA if Republicans win control of the Senate.
After the debate ended, Warren said in a tweet: "At the end of the day, Republican Scott Brown wants Mitch McConnell to run the Senate & Mitt Romney to run the White House."
But she didn't emphasize that argument consistently during the debate -- and she'll likely have to double down on that message.
Warren has led Brown in several polls released this week, while he held the lead in one released Thursday. The two will meet for three more debates this fall.