Zapata was a member of Movimiento Alternativa Republicana (Republican Alternative Movement)
Zapata was arrested on December 6, 2002 by agents of the Cuban police on charges of contempt, for which he was imprisoned for over three months. On March 20, 2003, 13 days after he was freed, he was arrested for a second time during a crackdown on dissidents and sent to the Kilo 7 prison in Camagüey. At the time of his arrest, he was participating in a hunger strike organized by the Assembly to Promote a Civil Society, taking place at the home of Marta Beatriz Roque Cabello. The hunger strike was meant as a petition for the release of several comrades.
He was charged with contempt, public disorder, and disobedience and sentenced to 36 years in prison after several judicial processes. As a result, Amnesty International recognized him as a prisoner of conscience, "imprisoned solely for having peacefully exercised [his] rights to freedom of expression, association and assembly". The socialist Monthly Review, in contrast, expressed skepticism of Amnesty's statement, alleging that Zapata was arrested and convicted several times on charges of fraud, firearm possession, and assault with a machete.
On either December 2 or 3, 2009, Zapata began a hunger strike as a protest against the Cuban government for having denied him the choice of wearing white dissident clothes instead of the designated prisoner uniform, as well as denouncing the living conditions of other prisoners. As part of his claim, Zapata was asking for conditions comparable to those that Fidel Castro had while incarcerated after his 1953 attack against the Moncada Barracks. For their part, the Cuban government stated he refused food because authorities wouldn't put a TV set, a stove and a phone in his cell.
During the hunger strike Zapata refused to eat any food other than his mother's, who visited him every three months. According to the U.S.-based opposition group Cuban Democratic Directorate, prison authorities then denied Zapata water, which led to his deteriorated health and ultimately kidney failure.
Zapata persisted in the hunger strike and was admitted to the Camagüey Hospital at an unspecified date, where he was given fluids intravenously against his will. On February 16, 2010 his condition worsened and he was transferred to Hermanos Ameijeiras Hospital in Havana, where he ultimately died on February 23, 2010 at approximately 3:30 pm EST.
It was the first time that an opponent of the Cuban government died during a hunger strike since the 1972 death of Pedro Luis Boitel.
On March 16, 2010 an open letter condemning the Cuban government for the unjust incarceration of Orlando Zapata Tamayo and asking for the release of other political prisoners was posted in an internet blog. In less than a week the letter had obtained over 30,000 signatures. Among the signatories are prominent intellectuals from both the left and right of the political spectrum.
President Raúl Castro took the "unprecedented step" of expressing public regret about the death of Zapata. During his remarks, he said Zapata was treated by top doctors and denied he was tortured. Cuban state television also aired a report where doctors who treated Zapata, said they tried to get him to eat, with Dr. María Ester Hernández stating:
"We explained to him the consequences of his decision at every turn and how much he was endangering his life with this. But he kept it up."
Cuban state newspapers, meanwhile, described Zapata as a "common criminal falsely elevated to martyr status."
The U.S. State Department stated that it was "deeply saddened" by Zapata's death, while the European Union called on Cuba to release its remaining political prisoners. Spain issued a statement remembering Zapata as a "human rights defender", while France expressed "dismay" and stated that its government had been lobbying Cuba on Zapata's behalf. The incident was seen as a significant setback for the thawing of Spanish-Cuban and U.S.-Cuban relations, with one analyst describing it as "the nail in the coffin of Spain's efforts to improve EU-Cuba ties".
On 23 February 2012, the Ladies in White met at the former home of deceased leader Laura Pollan to commemorate the second anniversary of Zapata's death. They were protested by a group of government supporters in coordination with security agents, who chanted "Down with the worms!" and "Long Live Raúl!"
Russian Historian Yuri Doykov dedicated his book to Orlando Zapata