Florida Senator Marco Rubio has dropped out of the race for the Republican presidential nomination after a humiliating defeat in his home state to Donald Trump.
Donald Trump, his party's front-runner, has 46% of the vote in Florida and is also leading in early results from North Carolina, Illinois and Missouri.
But Ohio Governor John Kasich has claimed victory in his home state over Mr Trump.
"While we are on the right side this year, we will not be on the winning side," Mr Rubio once the party establishment's favourite, told supporters in Miami.
On the Democratic side, former Secretary of State Hilary Clinton said she was "moving closer" to her party's nomination after projected triumphs in Florida, Ohio and North Carolina.
She is also leading in Illinois and Missouri against Vermont Senator Bernie Sanders according to early results.
"Our commander in chief needs to defend our country, not embarrass it," Mrs Clinton, 68, said in her victory speech, an apparent swipe at Mr Trump.
The Republican party establishment was hoping Mr Kasich could clinch his first victory by defeating Mr Trump in the Midwestern presidential bellwether of Ohio.
However, analysts say Mr Kasich currently has no path to the Republican nomination and his win could end up helping Mr Trump by dividing the vote against the brash New Yorker.
Mr Trump, 69, has only one other rival, arch-conservative Texas Senator Ted Cruz who did not seem on course for any victory on Tuesday.
Victory in Florida gives Mr Trump all 99 delegates and the Republican nomination looks to be his to lose, a possibility that seemed laughable to pundits only a year ago.
The party fears the property magnate - who has vowed to temporarily ban Muslims from entering the US, deport 11 million illegal immigrants and impose protectionist trade policies - will lead them to oblivion in November's White House election.
About two-thirds of Republican primary voters in all five states voting on Tuesday support the Muslim ban idea, according to exit polls by the Associated Press news agency.
Democratic President Barack Obama took a not-too-subtle jab at Mr Trump on Tuesday, saying he was dismayed by what was happening on the presidential campaign trail.
A candidate needs a majority figure of 1,237 delegates to secure the presidential nomination at the Republican party convention in July.
If no single candidate reaches that magic number, then the Republicans will face a contested convention.
This happens very rarely, forcing party members to keep voting until a winner emerges.
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