He made the announcement after conceding defeat to Donald Trump in his home state.
Mr Rubio implicitly rebuked the front-runner throughout a speech in Miami announcing he was dropping out of the race, imploring Americans to "not give in to the fear, do not give in to the frustration".
He accepted it "is not God's plan that I be president in 2016 or maybe ever".
Rubio was baptised Catholic and after exploring the Mormon and Southern Baptist faiths he is now a practicing Catholic.
He is known to have donated large sums of money to local churches in his state.
Elsewhere in the race for the Oval Office Donald Trump scored victories in three states but lost Ohio to state governor John Kasich.
Hillary Clinton won at least four states, dealing a severe blow to the bid by Bernie Sanders to slow her march towards the Democratic nomination.