Voters went to the polls in a dozen states and so far have handed seven wins each to Clinton and Trump. Clinton took Alabama, Arkansas, Georgia, Massachusetts, Tennessee, Texas and Virginia, while Trump won Alabama, Arkansas Georgia, Massachusetts, Tennessee, Vermont and Virginia.
Bernie Sanders, Clinton's insurgent Democratic rival, captured Colorado, Oklahoma, Minnesota and his home state of Vermont.
Cruz's Texas and Oklahoma victories, meanwhile, were crucial wins that gave him a rationale to carry on in the race. He pointed to those triumphs, combined with his victory in the Iowa caucuses, as proof that only he can actually beat Trump.
"After tonight, we have seen that our campaign is the only campaign that has beaten, that can beat and that will beat Donald Trump," Cruz told supporters.
But that argument was complicated when Rubio notched his first win of the election season in Minnesota. The Florida senator insisted in an interview with CNN that he will move forward and doesn't believe Trump will win the nomination.
"This is the fight for the heart and soul of the Republican Party," Rubio told CNN's Jake Tapper. "I will go through all 50 states before we stop fighting to save the Republican Party from someone like that."
Clinton victories
Clinton's victories in the South are further evidence of her strength among African-American voters, which could make it extremely difficult for Sanders to win the nomination.
"What a Super Tuesday," Clinton said at a rally.
Trump's victories help him stretch his lead in the GOP White House battle and underscore his growing support across all sectors of the Republican coalition. Those wins come despite Trump spending the past several days embroiled in a fight that has rival candidates and party elders, desperate to stop his march to the nomination, branding him unfit for the presidency.
"This has been an amazing night," Trump said in a victory speech.
Trump predicted that he would win the Florida primary in two weeks against Rubio, whom he called the state's "little senator" and a "lightweight."
Sanders, who is keen to challenge the growing narrative that the former secretary of state is now on track to win the nomination, hopes to halt the Clinton tide with his four victories.
"This campaign is not just about electing a president," Sanders said at a rally Tuesday night in Vermont. "It is about transforming America."
A total of 595 Republican delegates of the 1,237 needed to clinch the GOP nomination were up for grabs in 11 states. Sanders and Clinton faced off in 11 states for 865 of the 2,383 delegates needed to win the Democratic race.
Trump's confidence
In an unusual move that reflected his booming confidence, Trump held a rally in Ohio, a state that did not take part in Super Tuesday but holds a crucial winner-take-all primary in two weeks. He also stopped in Kentucky, where Republicans vote on Saturday. In the latest surreal twist to his increasingly bizarre showdown with Rubio, Trump said that he had "beautiful hands" after the Florida senator asked at an earlier rally why the real estate mogul's hands were so small.
Cruz, speaking to reporters before casting his ballot in Houston, did not wait for the results to roll in before signaling that he will try to nudge Rubio and John Kasich out of the race.
"If you want to beat Donald Trump, we've got to get to a head-to-head, one-on-one race," Cruz said. "What Donald is benefiting from is a fractured opposition."
But Rubio, who held Election Day rallies in Oklahoma and Minnesota, made it clear that he isn't going anywhere.
"I will campaign in all 50 states. I will get in my pickup truck and drive around this country if I have to before I allow the party of Lincoln and Reagan to fall into the hands of a con man," Rubio said, referring to Trump.
Trump, who has turned American politics upside down with his outsider campaign, nationwide media blitz and crusade against political correctness, went into the day with his polling hitting new peaks.
A national CNN/ORC poll published on Monday shows that Trump has lifted the ceiling on his support that for months hovered around 30% and now has the support of 49% of Republican voters, more than 30 points ahead of Rubio and Cruz.
Trump's surge has some senior party figures registering alarm that his presence at the top of the Republican ticket, given his controversial rhetoric and stances on issues like immigration, could cost the party not just the White House but control of the Senate as well.
"We can't have a nominee be an albatross around the down-ballot races," Republican Senate Majority Whip John Cornyn told CNN on Monday when asked whether he had concerns about the prospect of Trump winning the GOP race. "That's a concern of mine."
Exacerbating the fears of the party establishment, Trump struggled to extricate himself from a controversy that erupted after he initially failed to disavow the support of David Duke, a former leader of the Ku Klux Klan, during a CNN interview. Trump blamed a malfunctioning earpiece for the oversight but his rivals pounced.