Republican US presidential candidate Ted Cruz announces that he is dropping out of the 2016 race for the Republican presidential nomination as his wife Heidi looks on at his Indiana primary night rally in Indianapolis, Indiana, US, May 3, 2016. [Photo/Agencies]

Cruz had been counting on a win in Tuesday's primary to slow the New York businessman's progress toward the nomination. But Trump rode momentum from wins in five Northeastern states a week ago to wrest Indiana from Cruz, whose brand of Christian conservatism had been expected to have wide appeal in the state.

David Yepsen, director of the Paul Simon Public Policy Institute at Southern Illinois University, said the Republican race is over.

"Cruz is certainly young enough to fight again another day. Kasich's a serious guy but if stays in this he could look silly," Yepsen said.

The loss for Cruz was a sour ending to a rough day in which he got entangled in a harsh back-and-forth with Trump.

It began when the billionaire repeated a claim published by tabloid newspaper the National Enquirer that linked Cruz's father, Cuban emigre Rafael Cruz, with President John F. Kennedy's assassin Lee Harvey Oswald.