Vice President Nicolas Maduro called the violence tragic early Saturday on television and said the authorities had launched an investigation.
He and other officials did not give a death toll from the riot at Uribana prison in the central city of Barquisimeto.
The newspaper Ultimas Noticias reported on its website that 54 were killed. The television channel Globovision reported about 50 killed. Both cited Ruy Medina, the director of Central Hospital in the city, who also said that dozens were hurt.
Penitentiary Service Minister Iris Varela said earlier on television that the riot broke out when groups of inmates attacked National Guard troops who were attempting to carry out an inspection.
Varela said the violence had affected a number of prisoners and officials, but said the authorities would hold off until control had been re-established at the prison to confirm the toll. She said the government decided to send troops to search the prison after receiving reports of clashes between groups of inmates during the past two days.
The death toll provided by Medina rose late Friday after he had initially reported four killed and dozens injured.
Opposition leader Henrique Capriles condemned the government's handling of the country's overcrowded and violent prisons.
"Our country's prisons are an example of the incapacity of this government and its leaders. They never solved the problem," Capriles said on his Twitter account. "How many more deaths do there have to be in the prisons for the government to acknowledge its failure and make changes?"