Hundreds of public buses ferried young and old to the concert site, and the government laid on even more transportation, hoping for a large turnout.
Most concertgoers wore white - to symbolize peace - and some held up signs reading "Peace on Earth" and "We Love You Juanes."
Puerto Rican singer Olga Tanon opened the concert with a loud shout-out to the crowd.
"Together, we are going to make history," she said, as the plaza erupted in cheers.
Even before the show started, colorful umbrellas sprouted like flowers across the wide square as revelers shaded themselves from the unrelenting sun. Ambulances set up behind the stage treated those who had succumbed to dehydration and other ailments, many before a single note was played.
"We are going to stay as long as we have the strength," said Cristina Rodriguez, a 43-year-old nurse accompanied by her teenage son, Felix. They and thousands of others had arrived hours before the concert to get a good spot, ignoring government warnings not to turn up until noon.
"We've been here since three in the morning waiting for everyone, waiting for Juanes and for Olga Tanon," said Luisa Maria Canales, an 18-year-old engineering student. "I'm a little tired, but I am more excited."
That excitement does not extend to some across the Florida Straits, where Juanes has endured death threats, CD smashing protests and boycotts since his decision to hold the "Peace Without Borders" concert in Havana.
Police in Key Biscayne, Florida, say they are keeping watch over the homes of both the rocker and his manager, Fernan Martinez Maecha.
Still, the criticism from Florida is far from universal. Spanish-language stations covered the event and several exile groups have voiced support, describing it as a rare chance for Cubans to get a glimpse of the outside world.
Some Cuban officials have used the opportunity to deride U.S. foreign policy toward Cuba, and the 47-year trade embargo in particular. But Juanes has insisted the concert is about music, not politics.
"It is one more grain of sand for improving relations through art," the singer said upon arriving in Havana late Friday.
Of the threats from Miami, he said only: "It is a city that I love."
Juanes met recently with U.S. Secretary of State Hillary Rodham Clinton and the concert even prompted comment from President Barack Obama, who told the Spanish-language Univision network that the event probably wouldn't have much effect on U.S.-Cuban relations.
"My understanding is that he's a terrific musician. He puts on a very good concert," Obama said in the interview broadcast Sunday. "I certainly don't think it hurts U.S.-Cuban relations. These kinds of cultural exchanges - I wouldn't overstate the degree that it helps."
The show also features Cuban folk legend Silvio Rodriguez and salsa stars Los Van Van, as well as performers from Spain, Ecuador, Italy and elsewhere.
The festivities took place below a giant likeness of revolutionary icon Ernesto "Che" Guevara and near the heavily guarded offices of Fidel and Raul Castro.
Juanes, who has won 17 Latin Grammy awards, more than any other artist, is known for his social activism. His first "Peace Without Borders" concert in March 2008 drew tens of thousands to the border between Venezuela and Colombia when tensions were high over a Colombian commando raid into neighboring Ecuador that killed a leading rebel commander.
Some Cuban fans didn't even wait for the sun to rise. On Havana's seaside Malecon boulevard, thousands of partygoers gathered before dawn, drinking, singing and staring out at the moonlit sea. Nearly all said they planned to attend the show.
"I am singing to the Cubans, I am singing for you, Juanes," crooned Elide Ramirez, a Juanes fan, as he strummed on a guitar just after 5 a.m. "Here are the Cubans, waiting for you like brothers."