Brown has promised to use his position as the 41st Republican vote to kill of the healthcare changes pushed forward by Barack Obama, the US president.
Mitch McConnell, the senate Republican leader, said that Brown's victory was a clear sign that Americans had rejected Obama's healthcare proposals.
"I think you can make a pretty good argument that healthcare might be dead"
"They don't want this bill and want Washington to listen to them," he said.
"Americans are investing their hopes in good Republican candidates to reverse a year-long Democrat trend of ignoring the American people on the issues of healthcare, spending and the growth of government."
However, Harry Reid, the Democrat senate majority leader, said that politicians would continue to work towards healthcare reform.
"While Senator-elect Brown's victory changes the political math in the senate, we remain committed to strengthening our economy, creating good paying jobs and ensuring all Americans can access affordable health care," he said.
"We hope that Scott Brown will join us in these efforts."
Al Jazeera's John Terret reporting from Washington DC, said: It's important to understand that Obama is seen differently here in the US to how he is overseas.
"Looking in from overseas, he is erudite, articulate and professorial, a man concerned with many of the world's problems that perhaps the previous administration was not and the world welcomes that," he said.
Terret said: "There is very real anger among Americans at the rising level of joblessness, the cost of the healthcare reform being pushed through the congress, they're irritated with national security issues as embodied by Detroit's attack on Christmas day on the airliner, his own base is angry about sending more troops to Afghanistan.
"Blacks for example are irritated that he doesn't take about race issues more, Latinos are concerned that there hasn't been the promised immigration reform and of course Guantanamo Bay is still open - and it's that that Scott brown tapped into while the democrat candidate was aloof and distant."
Robert Gibbs, the White House spokesman, said that Barack Obama, the US president, had called Brown following his victory.
|Brown has pledged to kill off Obama's healthcare bill in the senate [AFP]
"The president congratulated Senator Brown on his victory and a well-run campaign," he said.
"The president told Senator Brown that he looks forward to working with him on the urgent economic challenges facing Massachusetts families and struggling families across our nation.
Earlier, Gibbs had said that Obama did not believe that Brown's election would stop the passage of the healthcare reform bill through the US Congress.
But following Brown's election, Anthony Weiner, a Democratic congressman, told MSNBC: "I think you can make a pretty good argument that healthcare might be dead."
With more than 80 per cent of the vote counted, Brown had a lead of five per cent over his rival, US news networks CNN and MSNBC reported.
"I am heartbroken at the result and I know you are also, but I know we will get up tomorrow and continue the fight," Coakley told supporters in the city of Boston.
"We wish [Brown] luck in his public service."
Toby Chaudhuri, a Democrat strategist, told Al Jazeera: "Its a stunning victory and there is no question that Scott Brown fought a very clever campaign.
"There is a very clear message for the Democrats and that is that they have to wake up," he said.
"There will be a lot of debate here in Washington about what this means, not only for healthcare reform but also for Obama's administration."
Edward Kennedy, the Democrat who held the Massachusetts seat for almost 47 years, died in August of brain cancer.
Fellow Democrat Paul Kirk was appointed by the state's governor in September to occupy Kennedy's seat and will remain in the senate until the winner is sworn in.
Massachusetts last elected a Republican to the senate in 1972, but the weak economy and doubts about Obama's healthcare overhaul appeared to have moved some voters to abandon party loyalties at a crucial juncture for the president and his Democratic party.
More broadly, the upset in Massachusetts raises the spectre of large losses for Democrats in midterm congressional elections in November.