Trump easily defeated rivals John Kasich and Ted Cruz in all five states that held contests, Pennsylvania, Maryland, Connecticut, Rhode Island and Delaware, with a margin of victory rivaling that of his home state of New York a week ago. He was on a path to winning the vote in every single county in each state.
Clinton, already in control of the Democratic race, defeated challenger Bernie Sanders in Maryland, Delaware, Pennsylvania and Connecticut. Her only loss of the night was to Sanders in Rhode Island.
The two front-runners used victory rallies to snipe at each other in the kind of back and forth that will take place should they win their party's presidential nominations and face off in the Nov. 8 election to succeed Democratic President Barack Obama.
"I think she's a flawed candidate and she's going to be easy to beat," Trump said at a news conference at New York's Trump Tower.
Trump, who is to deliver a foreign policy speech in Washington on Wednesday, criticized Clinton's record as secretary of state and her vote as a U.S. senator from New York in support of the Iraq war. He said her only advantage was as a woman seeking to become the first female U.S. president.
"Frankly if Hillary Clinton were a man, I don't think she'd get 5 percent of the vote," he said.
Clinton, in a victory speech in Philadelphia, took aim at Trump for accusing her of trying to "play the woman card."
"Well if fighting for women's healthcare and paid family leave and equal pay is playing the woman card, then deal me in," she said to cheers.
For the Republicans, the Northeastern battles set the stage for a big contest next week in Indiana. Trump has a small lead in polls in the state but Cruz appears stronger there. Trump needs a victory to get closer to the 1,237 delegates required to win the nomination.
Of 118 committed delegates available on Tuesday, the Associated Press said Trump took 105, raising his total delegates to 950. Kasich won five, all from Rhode Island, and Cruz one, with seven delegates still to be assigned. Pennsylvania's 54 unbound delegates will become clearer later.
Projecting confidence, Trump said it was time for Cruz and Kasich to get out of the race so the party can unify behind him. He also urged Sanders' voters to support him.
"I consider myself the presumptive nominee," he said, adding later: "As far as I'm concerned, this thing is over."
Although the race remains fluid, Trump's wins made it less likely that Republicans would choose their nominee at a contested convention in July in Cleveland, an outcome seen by Cruz and Kasich as their only chance at the nomination.
Cruz was already looking ahead to Indiana's Republican primary on May 3.
"I got good news for you: Tonight, this campaign moves back to more favorable terrain," the U.S. senator from Texas said in Knightstown, Indiana, inside the high school gymnasium made famous by the movie "Hoosiers," which celebrated underdogs.
APPEAL FOR UNITY
Clinton's strong showing in the Democratic race added to the pressure on Sanders to get out of the race or ease his criticism of her.
In her victory speech, Clinton gave a nod to Sanders and spoke of the need for party unity.
"Whether you support Senator Sanders or you support me, there is much more that unites us than divides us," she said.
Clinton's victories on Tuesday gave her 2,141 delegates, according to the AP, pushing her closer to the 2,383 needed for the nomination. Senate Democratic leader Harry Reid told reporters earlier on Tuesday he did not think Sanders, a U.S. senator from Vermont, had a realistic path to winning the nomination.
Sanders, in a speech in Huntington, West Virginia, and a subsequent statement, showed no signs of getting out of the race.
"The people in every state in this country should have the right to determine who they want as president and what the agenda of the Democratic Party should be. That's why we are in this race until the last vote is cast," he said in his statement.
Trump has consistently done well among lower-income voters and voters with only high school diplomas or less. But he performed well in the Northeastern region, which is the most highly educated in the country and also was strong across income levels.
In Maryland for example, Trump won 62 percent of supporters with some college education and 54 percent of college graduates. He won the support of more than half of Republicans in the state whose incomes were between $50,000 and $200,000 and also won a 46 percent plurality of Republican voters who earned $200,000 or more.