The Massachusetts lawmaker forced Senate colleague John Edwards on Tuesday to abandon his attempt for the nomination by taking nine of 10 party contests held from coast to coast on "Super Tuesday."
Kerry spoke by telephone with Edwards and received a congratulatory call from Bush before throwing down the gauntlet to the Republican incumbent.
"Tonight, the message could not be clearer all across our country, change is coming to America," he said in his victory speech.
Kerry ticked off a list of campaign promises, from repealing Bush tax cuts to health coverage and efforts to create new jobs. He reiterated accusations that Bush was conducting an "inept, reckless arrogant and ideological foreign policy."
For Kerry, a four-term senator and Vietnam war hero, the nomination capped a roller-coaster campaign that saw him go from front-runner to struggling underdog and back to the top again.
Kerry had kind words for Edwards, who has won praise for his courteous and unflaggingly positive campaign and has been touted as a possible vice-presidential candidate.
But Kerry gave no indication of his choice for running-mate ahead of the Democratic national convention this July in Boston.
Edwards, who had been under increasing pressure to throw in the towel, was to announce his withdrawal officially on Wednesday in North Carolina, which he represents in the Senate, said campaign staffers.
He stayed upbeat in a speech on Tuesday to supporters in Atlanta, Georgia, congratulating Kerry, but calling his own populist campaign "the little engine that could" which touched the souls of Americans.
Kerry, who had won 18 of the first 20 Democratic contests, nearly ran the table of Tuesday's votes with 1151 delegates at stake, more than half the 2162 needed to secure the nomination.
White House aides said Bush congratulated Kerry for an "impressive victory" and told him he was looking forward to a spirited race.
On Thursday, the Bush campaign plans to unroll a two-month media assault on Kerry - running adverts on cable television and targeting 17 states where the November race could be close.