Trump's supporters tried to drown out the protesters with chants of "USA! USA!"
"Equality! Equality!" chanted one protester as she was being removed from the event. Another said: "We are not the enemy. We need to unite so we can have policies to benefit the American people and their families. Keep families together. Stop the deportations."
"Don't hurt 'em. You can get 'em out, but don't hurt 'em," Trump said after the first wave of protesters interrupted him.
Pro-immigration activists from several groups organized a gathering outside the resort.
"Donald Trump is not welcome in Miami, this is our city," said Bertha Sanlés, a member of United Families, in a statement. "His words and the anti-immigrant hatred he has promoted against immigrant families like mine, do not make this country great. On the contrary, immigrants have made this country great with our hard work and our contributions."
Toward the end of his speech, Trump reiterated his call to build a wall along the U.S.-Mexico border, drawing cheers from the crowd.
"In this group, I wasn't so sure I should be talking about walls," he said.
The Republican White House hopeful is making his first campaign swing through Florida. On Saturday afternoon, he will head north to campaign in Jacksonville, where he has predicted some 15,000 people will turn out.
The real estate mogul took aim at several Democratic and Republican presidential rivals, including Hillary Rodham Clinton, Jeb Bush, Marco Rubio and Ben Carson. Carson, a soft-spoken retired neurosurgeon, has taken the lead over Trump in the key early state of Iowa, recent polls show.
Trump quipped that he informed Carson about his lead, "but he was sleeping."
Much of Trump's remarks centered on telling his supporters how well he is doing the polls.
"I'm winning Florida. I'm beating Bush and Rubio," he said to cheers from the crowd. Indeed, recent polls show Trump leading the two home-state Republican contenders.
Trump also defended remarks he made last week holding George W. Bush at least partly culpable for the Sept. 11, 2001, attacks. But he suggested that Bill Clinton deserves some blame as well.
"In all fairness to Bush, he was only president for about nine months," said Trump.
About four miles away from Jeb Bush's nondescript campaign headquarters, preparations for Trump's evening rally were well underway here hours before he took the stage.
"Hey guys, we're opening up the house!" an organizer yelled before throngs of supporters spilled into the room an hour and 45 minutes before of Trump's speech.
The first wave moved in swiftly, some running to the front of the room to position themselves nearest to Trump's podium as more waited outside.
"We need Trump!" the crowd chanted at one point. At another, a man started playing "When the Saints go Marching In" on his soprano saxophone.