Warren criticized Brown for procedural votes against a bill that would have prevented a doubling of federal student loans. Brown said he ultimately voted for a bipartisan measure that did not raise taxes.
Warren on several occasions accused Brown of using the same "playbook" as Republican presidential candidate Mitt Romney. Polls in Massachusetts have shown Obama with a wide lead over Romney.
Warren also invoked the late Sen. Edward Kennedy at one point in the debate, after Brown cited a study by the National Federation of Independent Businesses that "Obamacare" would cost 17,000 jobs in Massachusetts.
Warren said the NFIB was a group that had endorsed Republicans, including Brown, and once "referred to Ted Kennedy as public enemy number one."
Brown was elected to fill the seat left vacant by the death of Kennedy in 2009.
One notable topic that failed to surface was the controversy surrounding Warren's claims of Native American heritage that led off the first two debates.
Brown said he didn't raise the issue because, unlike the first two debates, he wasn't asked about it.
Wednesday's debate was their first in Western Massachusetts.
LeBlanc reported from Boston.
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