Cuba's President Raul Castro says nearly all death sentences are to be commuted to prison terms of between 30 years and life.
It is the latest in a series of liberalising measures. Mr Castro said the decision was humanitarian and not due to international pressure.
Three people charged with terrorism will stay on death row for the time being. Their cases will be reviewed.
The death penalty will remain on the statute book in Cuba.
Mr Castro also announced he was convening a Communist Party congress next year - the first for more than a decade.
The congress is expected to chart Cuba's future political and economic agenda.
Cuba has been under pressure from human-rights organisations to abolish the death penalty, which is carried out by firing squad.
There are no official figures, but the Cuban Human Rights Commission estimates that between 40 and 50 inmates could be affected.
The only exceptions to the death penalty changes are two Central Americans charged with a hotel bombing that killed an Italian tourist, and a Cuban American charged with murder during an attempt at armed infiltration of the island.
"It would be irresponsible and disingenuous to renounce the dissuasive power that capital punishment has on the real terrorists, the imperialist mercenaries," Mr Castro said in a speech to the Communist Party central committee.
This is the latest in a series of social changes announced by Raul Castro since taking over as president from his older brother Fidel in February. They are designed to make life easier and less restrictive for ordinary Cubans.
They include lifting the ban on owning mobile phones and staying in the same hotels previously reserved for foreigners.
Buying and selling property is still not allowed, however.
Fidel Castro retired earlier this year after undergoing a series of intestinal operations in July 2006.