The 90-minute primetime debate, which saw Clegg depict himself as a fresh-faced honest alternative to the status quo, was the first in a series of three US-style confrontations between the party leaders ahead of the May poll.
The leaders clashed on issues like the economy, health care, law and order, immigration and political corruption.
Preaching a message of "fairness," Clegg said the Liberal Democrats offered "something different". "Do not let anyone tell you that the only choice is the old politics," he said.
"Say 'yes' to something new," he urged voters, insisting that Labour and the Conservatives had made the "same old mistakes over and over again".
"Despite all the problems and challenges we have, we can be hopeful about the future if we chose something different," Clegg said.
Tory leader David Cameron promised "change" while Prime Minister Gordon Brown (Labour) offered "prosperity for all".
Papers declare Clegg winner
The Friday papers generally concluded that the head of the Liberal Democrats, the UK's third biggest party, won the contest, which focused on domestic affairs.
Polls of viewers published after the debate also suggested that Clegg had come out on top.
A YouGov poll put the Lib Dem leader on 51%, far ahead of Cameron on 29% and Brown on 19%. An ITV/Com Res poll suggested 43% of viewers thought Clegg won, with 26% opting for Cameron and 20% for Brown.
But the biggest winners of the evening were the voters, who were treated to the sight of British prime ministerial hopefuls clashing on live TV for the first time.
"British politics will never be the same again," the Times newspaper announced, concluding that the debate had offered "an extraordinary, sometimes electrifying, spectacle".
Labour claimed that Prime Minister Gordon Brown had been "very substantial," while the Tories said opposition leader David Cameron was "strong and personal".
Clegg, who confidently spoke directly to the camera rather than to his rivals, said "there is an alternative to the two old parties. I know many of you think that all politicians are just the same. I hope I've tried to show you that that just isn't true".
Economy takes centre stage
The economy will be at the forefront of voters' minds when they head to the polls in May, with Britain in the throes of its worst recession in years.
Brown declared that "the Conservatives are a risk to the economy in this country," while Cameron claimed that proposed Labour hikes to national insurance contributions were merely "a tax on jobs, a jobs killer [and] an economy killer".
Clegg, meanwhile, set his sights on bankers. "A greedy banker in the City of London pays lower taxes on their wages than a cleaner does," he claimed.
Regarding the parliamentary expenses scandal which rocked UK politics last year, Brown said he had been "shocked" and "sickened" by the revelations, while Cameron described it as "a horrendous episode".
Many observers noted that the Liberal Democrat leader appeared more comfortable with the debating format than the other leaders. "The more they [Brown and Cameron] attack each other, the more they sound exactly the same," he said at one point.
Brown sought to press home his advantage over his opponents in terms of experience. "I know what this job involves," he said.
Cameron, meanwhile, accused his rivals of trying to "frighten" voters about a Tory government with scare stories about spending cuts, urging voters to "choose hope over fear".
Last night's debate, which broadcaster ITV said had been watched by "an audience of millions," was keenly followed online, with estimates suggesting that 100,000 Tweets were posted within the first hour.
Later debates will focus on international affairs (Sky News; 22 April) and economic affairs (BBC One; 29 April).
