The magnitude 7.0 quake, whose epicenter was inland and only 10 miles from Port-au-Prince, sent panic-stricken people screaming into the streets of the city, as a cloud of dust and smoke from falling buildings rose into the sky.
As darkness fell amid scenes of chaos and anguished cries from victims, residents desperately tried to dig out survivors or searched for missing relatives in debris-strewn streets.
The presidential palace was among the buildings damaged, Haiti's ambassador to the United States, Raymond Alcide Joseph, told CNN.
"My country is facing a major catastrophe," he said.
Haiti is the poorest country in the Western Hemisphere and has a history of destructive natural disasters. Some 9,000 U.N. police and troops are stationed there to maintain order.
The major quake, followed by several aftershocks, prompted a tsunami watch for parts the Caribbean but this was later canceled.
"Everything started shaking, people were screaming, houses started collapsing ... it's total chaos," Reuters reporter Joseph Guyler Delva said in Port-au-Prince.
"I saw people under the rubble, and people killed," he added, saying he had witnessed dozens of casualties.
U.S. President Barack Obama said his "thoughts and prayers" were with the people of Haiti and pledged to come to their aid. The Obama administration said the State Department, USAID and U.S. military were working to coordinate assistance.
The United States "will be providing both civilian and military disaster relief and humanitarian assistance," Secretary of State Hillary Clinton said.
A local employee for the charity Food for the Poor reported seeing a five-story building collapse in Port-au-Prince, spokeswoman Kathy Skipper told Reuters.
Another Food for the Poor employee said there were more houses destroyed than standing in Delmas Road, a major thoroughfare in the city.
"Within a minute of the quake ... soil, dust and smoke rose up over the city, a blanket that completely covered the city and obscured it for about 12 minutes until the atmospheric conditions dissipated the dust," Mike Godfrey, who works for USAID, told CNN from the city.
Experts said the quake's epicenter was very shallow at a depth of only 6.2 miles, which was likely to have magnified the destruction.
PEOPLE SCREAMED 'JESUS, JESUS'
Speaking to CNN from Port-au-Prince, Ian Rogers of the charity Save the Children said he could hear cries of anguish and mourning rising up from around the city in the darkness.
Homes and buildings built on hillsides had come crashing down along with earth and rubble.
"All the roads currently are blocked," Rogers said.
"People were screaming 'Jesus, Jesus' and running in all directions," Delva said.
The Hotel Montana in Port-au-Prince, where many foreigners stay, suffered at least some minor damage.
A group of 12 U.S. students from Lynn University in Florida were visiting Haiti with Food for the Poor and some were able to send text messages to say they were fine, Skipper said.
The powerful quake was felt in southeastern Cuba, about 160 miles from the epicenter. Cuban authorities evacuated coastal residents because of the initial tsunami threat.
"I was seated on the terrace and I thought my chair had slid out from under me but I realized it was an earthquake," said Eduardo Machin, a resident of the coastal city of Santiago de Cuba. "It was very strong."
Sailors at the U.S. naval base at Guantanamo Bay in eastern Cuba felt the quake but there was no damage to the base or the detention camp where the United States holds 198 foreign terrorism suspects, said Chief Petty Officer Bill Mesta.
"It just shook a number of the buildings," Mesta said. "It felt like there was a strong gust of wind up against the building."
The base has stockpiles of blankets, tents and other relief supplies on hand for emergency use in case of mass disasters in the Caribbean. Personnel had begun checking the goods in anticipation that they will be asked to help in the relief effort, Mesta said. (Additional reporting by Alister Bull, Jane Sutton, Phil Barbara, Jeff Franks, Writing by Sandra Maler and Pascal Fletcher; Editing by John O'Callaghan)