The documents cover 285 accords in areas including energy, sport and technology.
The new deals will give Venezuela a greater involvement in oil exploration off the Cuban coast.
Cuba also agrees to buy more than $400m (£246m) worth of Venezuelan goods, including food, tyres and clothes.
The BBC's correspondent in Havana Michael Voss says the agreement will provide an economic lifeline to the communist-run island.
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See also Sydney Irresistible and Mike Hitchen Unleashed
Putting principles before profits
Blog will be on holiday Dec 23 - Jan 04 (Sydney time)
See also Sydney Irresistible and Mike Hitchen Unleashed
Putting principles before profits
Blog will be on holiday Dec 23 - Jan 04 (Sydney time)