McCain won nine states, including California and New York, according to projections, while his closest rival Mitt Romney could only take six.
As victory in many Republican state contests means that the winner secures all the delegates in that state, McCain has surged ahead of his competitors.
Mike Huckabee, who has been a distant third in the Republican race, took five states in Tuesday's vote, mainly in the south of the country.
"Tonight, I think we must get used to the idea that we are the Republican Party frontrunner for the nomination," McCain said in a speech to his supporters in Scottsdale, Arizona.
All the contenders from both parties took at least five wins, highlighting the tough road ahead for the presidential hopefuls.
A new round of contests in a half-dozen states are set for the weekend and in the coming week.
States won by Democratic and Republican candidates, based on projections:
Hillary Clinton: Arkansas, Arizona, California, Massachusetts, New Jersey, New York, Oklahoma, Tennessee (8)
Barack Obama: Alabama, Alaska, Colorado, Connecticut, Delaware, Georgia, Idaho, Illinois, Kansas, Minnesota, Missouri, North Dakota, Utah (13)
John McCain: Arizona, California, Connecticut, Delaware, Illinois, Missouri, New Jersey, New York, Oklahoma (9)
Mitt Romney: Colorado, Massachusetts, Minnesota, Montana, North Dakota, Utah (6)
Mike Huckabee: Alabama, Arkansas, Georgia, Tennessee, West Virginia (5)
According to figures from AP, Hillary Clinton now has 845 delegates of the 2,025 needed to secure the Democratic nomination, just ahead of Obama on 765.
Meanwhile McCain now holds 613 delegates out of a total of 1191, while Romney has 176, and Huckabee holds 142, AP said.
Clinton advantage is
partly due to her lead among so-called superdelegates, members of congress and other party leaders who are not selected in primaries and caucuses and who are also free to change their minds.
McCain is also in a commanding position in his attempt to take the 1,191 delegates needed to win the Republican nomination.
He has battled to win over conservatives in the party, who are uneasy with his relatively liberal views on immigration and tax cuts.
Huckabee won support from evangelical Christians, and he split votes with Romney among conservatives unhappy with McCain.
"A lot of people have been trying to say this is a two-man race," Huckabee told supporters in Little Rock, Arkansas.
"Well, you know what, it is and we're in it."
More than half the total delegates to the Democratic convention in August and about 40 per cent of the delegates to the Republican convention in September will be distributed from Tuesday's vote.
|Clinton took New York and California, states|
with the highest number of delegates [AFP]
Sir Robert Worcester, founder of the opinion polling company MORI, told Al Jazeera that many Republican voters may have chosen not to cast their ballot due to the strong performance of McCain in previous contests.
"All polls are saying McCain's got a good lead; he's going to be the Republican nominee so a lot of people will not have bothered to vote... The Democrats are going to unite in getting the Republicans out of the White House."
Gary Wasserman, a pollster from Georgetown University, said there were signs that the Democratic contest had energised voters more than the Republican battle.
"John McCain's vote total is less than both Democratic leaders ... He's got about three million votes in this Super Tuesday whereas both Obama and Hillary have gotten more votes than he has," he told Al Jazeera.
"The tendency in the Republican party is to rally around the leader, they tend to want to unify."
Concerns over falling housing values, rising prices and unstable financial markets were the biggest concerns of voters in both parties, exit polls showed.