Soltren has been on the run ever since, the FBI said. He remained jailed Tuesday after a brief appearance before a federal magistrate judge in Manhattan.
It was November 24, 1968 when prosecutors said the men used guns and knives to raid the cockpit and commandeer the flight on the way to Puerto Rico. A woman had smuggled guns and knives onto the plane in a diaper bag.
"As the 1968 charges allege, he terrorized dozens of passengers when he and his cohorts wielded pistols and knives to hijack Pan American flight 281," said Preet Bharara, the United States Attorney for the Southern District of New York. "The passage of time does not dull our resolve to bring fugitives like Peña Soltren to justice."
An FBI spokesman declined comment.
Two others pleaded guilty to air piracy and conspiracy to kidnap charges. A fourth man was acquitted and charges against the woman were dropped.
Soltren is expected to be arraigned on the charges if federal court on Tuesday.
There were nearly a dozen hijackings and attempted hijackings of American airliners to Cuba in 1968. Terrorism and extortion among the motives at the time when Cuban-American relations were severely strained.