Castro's remarks came during a six-hour speech that lasted until 4 a.m. Saturday and closed an international globalization conference in Havana attended by hundreds of economists.
"If Chavez is assassinated, the responsibility will lie entirely with the president of the United States," Castro said, neglecting to provide details, but noting that President Bush has encouraged Chavez's opponents in the past.
The Cuban leader said Chavez's left-leaning "revolution" threatens the interests of powerful people who tried to oust him with a short-lived coup in 2002 and several political campaigns against him.
An eventual attempt to kill Chavez would aim to halt the changes happening in the South American nation, Castro said — the same way the United States and others tried to eliminate him as he turned Cuba into a socialist country.
"With me they've already lost their time, this has become too advanced," the 78-year-old said of the Cuban revolution. "But that (the situation in Venezuela) is in a crucial stage."
Countless assassination plots against Castro and his closest advisers have been disclosed throughout the more than four decades of his rule.
Chavez on Saturday thanked the Cuban leader for his remarks.
"Thank you Fidel, it is true there are rumors, it is true there is information," he said while visiting areas affected by heavy rains outside Caracas.
"They are not going to succeed, my dear friend, you will see they will not," he added the 50-year-old. "I will become an old man, like you."
Ties between Chavez and the Bush administration soured after Washington's initial endorsement of a 2002 coup that briefly ousted Chavez.
Chavez has repeatedly accused American officials of working to undermine his government and of seeking to derail efforts at regional integration, charges which Washington has denied.
The close relationship between Castro and Chavez has irked many in Washington. Venezuela provides much of Cuba's oil on favorable terms, and Cuba has sent thousands of health care workers, teachers and sports trainers to poor neighborhoods in Venezuela to bolster Chavez's government.
While Castro devoted much of his speech to Chavez, he also said that after a decade of crisis Cuba's economy was finally stable, and that the centralized economic system was here to stay.
"Cuba is well," he said. "We have become more and more revolutionary, we have achieved many things."