Ortega, still president of the confederation of Venezuela workers, led a two-month general strike launched in 2002 that nearly shattered the nation's vital oil industry in a failed effort to oust Hugo Chavez, the Venezuelan president.
Raul Baduel, the defence minister, said on Sunday that Ortega had escaped from the Ramo Verde military prison along with three military officers.
He said: "There has been verification of the escape of these four citizens that I have mentioned."
Two of the officers had been convicted for military rebellion, while the third was awaiting trial for stealing property belonging to the military, Baduel said.
He said the government was conducting operations at ports and airports to ensure the four did not leave the country.
The labour leader was convicted last December of rebellion in connection with his role in the strike, which ended in early 2003.
He had been given political asylum in Costa Rica that year following accusations that Chavez was seeking to kill him.
But he returned to Venezuela, maintaining a low profile, and was reportedly working to unseat Chavez when he was captured in March 2005 in a Caracas nightclub.
Opposition leaders call his conviction an example of political persecution, and accuse the leftist Chavez of seeking to clamp down on dissidents.
Ortega helped lead a total of four national strikes against Chavez between 2001 and 2003, one of which came just before a coup that briefly ousted the firebrand leader in April 2002.
Chavez survived the coup and the strikes, and is now widely expected to be re-elected in a vote on December 3.