Céspedes was a landowner and lawyer in eastern Cuba, near Bayamo, who purchased La Demajagua, an estate with a tobacco plantation, in 1844 after returning from Spain. On October 10, 1868, he made the Grito de Yara (Cry of Yara), declaring Cuban independence, which began the Ten Years' War. That morning, after sounding the slave bell that indicated to his slaves it was time for work, they stood before him waiting for orders, and Cespedes announced they were all free men, and were invited to join him and his fellow conspirators in war against the Spanish government of Cuba. For this, he is called Padre de la Patria (Father of the Country). In April 1869 he was chosen President of the Republic of Cuba in Arms.

The Ten Years' War was the first serious attempt to achieve independence from Spain, and to free all slaves. The war was fought between two groups. In the East of Cuba the tobacco planters and farmers, joined by mulattos and some slaves, fought against the West of Cuba, with its sugarcane plantations (which required many slaves) and the forces of the Spanish Governor General. Hugh Thomas summarises thus: The war was a conflict between criollos (creoles, born in Cuba) and peninsulares (recent immigrants from Spain). The Spanish forces and the peninsulares, backed by rich Spanish merchants, were at first on the defensive, but in the longer run their greater resources told.

Céspedes was deposed in 1873 in a leadership coup. Spanish troops killed him in February 1874 in a mountain refuge, as the new Cuban government would not let him go into exile and denied him an escort. The war ended in 1878 with the Pact of Zanjón. The pact did make concessions: liberation of all slaves and Chinese who had fought with the rebels, no action for political offences; but not freedom for all slaves, and no independence. The Grita de Yara had achieved something, though not enough; but it had lit a long-burning fuse. Lessons learned there were later put to good use in the Cuban War of Independence.

Céspedes was married twice. The first to Maria del Carmen de Cespedes y del Castilo and they had Maria del Carmen, Oscar, and Carlos Manuel de Cespedes y Cespedes. He married the second time to Ana Maria de Quesada y Loinaz (1842 – 1910) and they had 3 children, Gloria (1871 – ?), Oscar and Carlos Manuel de Céspedes y Quesada (1871 – 1939), who was briefly President of Cuba after Gerardo Machado was deposed in 1933. In San Lorenzo before he died, Carlos Manuel met a widow, Francisca (Panchita) Rodriguez. Carlos Manuel and Panchita became lovers and produced a son, Manuel Francisco de Cespedes y Rodriguez.

He named Oscar, his fifth son, after his late second child Oscar, who was shot by a Spanish firing squad. The Spanish authorities wanted to exchange Oscar's life for Cespedes' resignation as President of the Republic of Cuba. He famously answered that Oscar was not his only son, because every Cuban who had died for the revolution he started, was also his son.

He had been, before the conflict, something of a musician, and he was part-composer of a romantic song called La Bayamesa.

His portrait was on the 10 pesos bills in Cuba until 1960 when it was moved to the 100 pesos bill. A municipality in Camagüey Province, Carlos M. de Cespedes was named after him.