In a statement, his family said he died in hospital in Bangkok on Monday.
Samak led the People Power Party (PPP) to victory in Thailand's first elections after a military coup that ousted his ally, former prime minister Thaksin Shinawatra, just over a year earlier.
His eight months in power were among the most turbulent in Thailand’s recent history.
As a friend and ally of Thaksin, Samak was accused by opposition groups - especially the "Yellow Shirt" movement - of being a proxy for the exiled former leader.
After his appointment, the "Yellow Shrts" mobilised massive demonstrations against his government, culminating in him being forced out of his own office in Bangkok’s Government House by tens of thousands of protesters.
Prior to his removal, he declared a state of emergency with the goal of restoring order to the streets of Bangkok, but the order was ignored by the armed forces.
Thaksin, who is living in exile to avoid a jail term for corruption, posted his condolences at Samak's death via a message on the Twitter service.
"My family and I express profound sorrow for the passing away of HE (His Excellency) Samak but I will not be able to attend his funeral," Thaksin said.