A total of 12 states from Alabama to Alaska are holding primaries or caucuses today. Virginia was the first state to open its polling stations at 6:00 AM (16:30 IST).
A new nationwide poll released yesterday said each of them were well ahead of their closest rivals on the eve of the 'Super Tuesday' showdown.
Trump has expanded his lead over the diminished field to capture the support of nearly half of Republican voters, while Clinton tops Bernie Sanders by nearly 20 points on the Democrat votes, according to a CNN/ORC poll.
Trump's rivals, Senators Marco Rubio and Ted Cruz, were desperately trying to halt his march toward nomination.
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If Trump wins the South, it could be lights out for his Republican challengers. Texas is the largest prize today.
Almost 600 Republican delegates are up for grabs today, nearly half the 1,237 needed to secure the nomination.
The 'Super Tuesday' is the biggest day of the 2016 US presidential primary primary season, with 12 states and one territory participating: Alabama, Arkansas, Colorado, Georgia, Massachusetts, Minnesota, Oklahoma, Tennessee, Texas, Vermont, Virginia, Wyoming and American Samoa.
Some 865 Democratic delegates are at stake, 36 per cent of those needed to win.
The presidential election is scheduled for November 8.