The government-organized march brought the Cuban capital to a standstill. Marchers swarmed along the seafront Malecon boulevard and past the US building carrying small Cuban flags as they shouted "Bush, Fascist!" and "Cuba will triumph with the truth!"
President Fidel Castro, 79, wore his trademark olive-green uniform but did not take his traditional place at the front of the march.
Instead Nicaragua's former Marxist Sandinista leader Daniel Ortega, a strong contender in upcoming Nicaraguan presidential elections, lead the march instead.
Marchers wore read T-shirts with a picture of Luis Posada Carriles, a Cuban exile and former CIA asset wanted on terrorism charges for blowing up a Venezuelan airliner in 1976, which killed 73 people. The picture was in a circle with a slash over it, emblazoned with the words "Warning - murderer."
State media reported that 1.4 million people joined the protest. Castro was also outraged by a rolling screen on the US Interests Section building that displays a mix of texts, including quotes from the Universal Declaration of Human Rights and sayings by civil rights leaders Martin Luther King and Mahatma Gandhi.
It also flashes brief news items which US officials say are a bid to subvert the strict censorship in Cuba's state media.
In his speech, Castro branded the electronic billboard a "provocation" by the US administration -- only to see it be switched on as he spoke.
"They have lit up the billboard," stormed Castro. "They are so courageous, these cockroaches. It seems little Bush gave them the order," he said, referring to US President George W Bush.
Castro also blasted Washington over Posada Carriles case. Washington "wants to set free the terrorist Luis Posada Carriles, which authorities in that country, including the father of the current president [a former CIA director], trained to commit monstrous crimes against the people of Cuba," he said. "Bush, you fascist, condemn the terrorist!" the crowd chanted.
US immigration authorities are holding Posada Carriles after he illegally snuck into the United States from Mexico.
In Washington, the US State Department dismissed the event as a "protest against freedom."
The event was held on the same day as a mass march of activists from across the Americas in Caracas that kicked off the six-day World Social Forum.
The annual anti-globalization forum is designed as a counterpoint to the World Economic Forum of political and business leaders that gets underway in the Swiss ski resort of Davos on Wednesday.
Castro has regularly used giant demonstrations outside of the US Interests Section in Havana to vent his anger at Washington, which has maintained an economic embargo against the island nation since 1962.
The United States and Cuba do not have full diplomatic relations, but maintain interest sections in the other's capital.