"Thank you Indiana!" Trump tweeted as the race was called in his favour yesterday.
Based on 13 per cent of precincts reporting, the billionaire frontrunner took 53.8 per cent of the vote, streets ahead of his nearest rival Ted Cruz on 33.9 and John Kasich on 9.4 per cent.
The Democratic race between Hillary Clinton and Bernie Sanders was still too early to call in the Midwestern state, but early voting results showed the former secretary of state with a razor-thin lead against her rival.
But yesterday's contest is seen as a day of reckoning for the "stop Trump" movement led by Cruz -- who has performed well in primaries dominated by conservative and evangelical voters, and was given a strong chance in Indiana.
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Cruz was hoping to use Indiana as a firewall, blocking Trump from receiving the 1,237 delegates necessary to secure the nomination at the Republican convention in Cleveland in July.
"Lyin' Ted Cruz consistently said that he will, and must, win Indiana. If he doesn't he should drop out of the race-stop wasting time & money," Trump tweeted.
If Trump sweeps Indiana's 57 delegates, the Cruz camp has admitted it faces an extremely steep road ahead.