A magnitude 7.2 earthquake hit about 160km west of Caracas, followed less than a minute later by a magnitude 7.5 tremor, according to the US Geological Survey (USGS).
"High casualties and extensive damage are probable and the disaster is likely widespread," the USGS said, initially estimating the death toll would most likely range from 10,000 to 100,000.
Three people were killed in the Baruta district in Caracas after two buildings collapsed, the district mayor said on social media. One person was killed and four buildings had completely collapsed, Gustavo Duque, the mayor of Chacao district in Caracas told journalists. Twenty-two people had been moved to hospital.
"We have buildings, homes and houses which have collapsed and we are taking care of things with everything we have available in terms of security, civil assistance," Interior Minister Diosdado Cabello said on state television. "The fire department, police all have been activated."
Video footage showed emergency workers climbing through the ruins of a collapsed building in the capital as night fell and distraught relatives seeking help for loved ones.
Interim President Delcy Rodriguez declared a state of emergency in the South American nation and requested funds from multilateral organisations to back the recovery effort.
"We extend our condolences to those who have unfortunately suffered the loss of a family member," she said in a national address, without giving a national count for deaths or injuries.
President Donald Trump said the US was ready, willing and able to help in the disaster.
"The two major earthquakes that just hit the great people of Venezuela are both massive in scale and have left a devastating number of deaths," Trump said.
Many Venezuelans were at home when the quakes struck during a public holiday marking an 1821 military victory that helped secure the country's independence from Spain.
"As soon as it started, we began hearing people screaming," said Astrid Ramirez, a 41-year-old publicist in western Caracas. "Everyone was running down the stairs."
Residents across Caracas, which was also hit by a deadly magnitude 6.3 earthquake in 1967, rushed to evacuate as buildings shook.
"There was a very loud crash. Things fell in the house, jugs inside the refrigerator. I've never experienced anything like it," said Coro Martinez, 56, who lives in eastern Caracas.
Maria Romero, an 80-year-old pensioner in southern Caracas, said police helped her get out of her home.
"This earthquake was horrible, even worse than the one in 1967," she said.
Another resident, a 41-year-old office worker who declined to be named, said she received an earthquake alert on her phone just before the shaking intensified.
"It was a normal afternoon, and suddenly my phone sounded an earthquake alert," she said. "As I picked it up and started listening to what it was saying, I first felt light shaking. Then, in less than two seconds, everything started moving."
Fire trucks were seen on the streets of Caracas, where some buildings suffered significant facade damage.
Video filmed at the Hospital de Clinicas Caracas showed a darkened hallway with ceiling panels hanging by cables and pieces of plaster scattered across the floor.
Other videos on social media appeared to show significant damage at Venezuela's main airport, while residents reported collapsed buildings in La Guaira, a coastal city near Caracas. Reuters could not immediately verify the footage from the airport and La Guaira.
The US Tsunami Warning System issued a tsunami threat for Puerto Rico and the US and British Virgin Islands after the earthquake, and said hazardous waves could also affect Aruba, Curacao and Bonaire. The warning was withdrawn about an hour later.
An estimated 30,000 people were killed when a quake caused widespread destruction in the cities of Merida and Caracas in March 1812, according to the USGS.
with AP and DPA
