The diplomats have until Wednesday to leave the country, President Nicolas Maduro said in a fiery speech after charging them with meeting with members of the Venezuelan opposition and plotting to "sabotage the electrical grid" and disrupt the economy.
"Get out of Venezuela! Yankee go home!" Maduro shouted on live TV as he announced the expulsions at a military event.
"I don't care what actions Barack Obama's government takes," he said.
A U.S. official said Venezuelan officials in Washington would be expelled in return.
"We will reciprocate," the official was quoted by The Wall Street Journal as saying.
The U.S. Embassy in Caracas said: "We completely reject the Venezuelan government's allegations of U.S. government involvement in any type of conspiracy to destabilize the Venezuelan government."
The top diplomat ordered to leave is Charge d'Affaires Kelly Keiderling, who runs the embassy in the absence of an ambassador in Caracas. Keiderling, who has held the post since 2011, was previously chief of staff of the State Department's Iraq office, her State Department biography says.
The other expelled diplomats are Vice Consul David Moo and Elizabeth Hoffman, an official in the embassy's political section.
Maduro publicly accused Hoffman shortly after assuming office April 19 of meeting with opposition figures to plot sabotage of the electrical system.
"These officials spend their time meeting with the Venezuelan extreme right wing, financing them and encouraging them to take actions to sabotage the electrical system, to sabotage the Venezuelan economy," Maduro said Monday in his TV address.
Maduro has often accused plotters of being responsible for a variety of the nation's ills, including electrical blackouts, The New York Times says.
Maduro was elected by a narrow margin in a special election to replace longtime President Hugo Chavez, who died of cancer March 5.
Chavez had pressed for the normalization of relations with the United States in his final months.
Hours after announcing Chavez's death, Maduro kicked out two U.S. military attaches, saying they tried to recruit Venezuelan military personnel to conspire against the government.
Venezuela suffers from one of the world's highest inflation rates and chronic shortages of basic consumer goods, including toilet paper.
Foreign Minister Elias Jaua said on television after Maduro's address the U.S. diplomats met in recent weeks with democracy advocates, union members and opposition elected officials who he accused of planning to destabilize the country.
The U.S. Embassy said the meetings were part of the officials' "normal diplomatic engagements."
"We maintain regular contacts across the Venezuelan political spectrum," the embassy said.
The expulsion announcement came as National Assembly President Diosdado Cabello was to travel to Moscow to strengthen diplomatic ties with Russia, Venezuelan newspaper El Universal reported.