While voting was reported to be light statewide, Kerry, who hadn't had an opponent in the primaries since 1984, was defeating political newcomer Ed O'Reilly, a lawyer, in virtually every community with about half the votes counted, The Boston Globe reported.
Kerry will face Republican Jeff Beatty in November's general election as he goes after a fifth term.
"Good news tonight. No. 1, we won this primary," Kerry said in claiming victory. "And No. 2 -- and frankly probably a lot more important -- there are only 128 more days of George Bush."
Sen. Edward Kennedy, D-Mass., who is fighting brain cancer, expressed support for his colleague after casting his vote in Hyannis.
"I look forward to returning to the United States Senate with John Kerry in January as we work to get our economy moving again, bring healthcare to all, restore America's standing in the world, and end the war in Iraq," Kennedy said in a statement.
Kennedy also expressed gratitude to well-wishers who have contacted him during his treatment.