State Attorney General Martha Coakley conceded just after 9 p.m. EST, little more than an hour after the polls closed, The Boston Globe reported. She entered the race seemingly almost certain of victory, only to be defeated by Brown, a little-known state senator when he declared his candidacy.
With most of the precincts reporting, Brown had 52 percent of the vote to 47 percent for Coakley.
Brown, who has promised to be the 41st vote to keep healthcare off the Senate floor, was triumphant, the Boston Herald said.
"I bet they can hear this cheering all the way to Washington, D.C.," he told reporters as he claimed victory.
"Tonight the independent voice of Massachusetts has spoken," he said. "I am ready to go to Washington without delay."
Brown's victory in one of the most heavily Democratic states in the country is an embarrassment for President Barack Obama, The Boston Globe said. It could derail the Democratic healthcare bill since Brown's election deprives the president and congressional Democrats of the 60th vote in the Senate needed to block a Republican filibuster.
"Tonight, Scott Brown made history by exceeding all expectations and defeating Martha Coakley in the heart of the (Democratic) Party's political stronghold," Republican National Committee Chairman Michael Steele said.
The last time Massachusetts sent a Republican to the U.S. Senate was 1972, when Edward Brooke won a second term. The seat Brown won Tuesday had been held by a Democrat since 1952, when a young congressman, John F. Kennedy, ousted Henry Cabot Lodge Jr.