In 1508, Sebastián de Ocampo sighted a bay that the indigenous population called Guanima. Now known as the Bahía de Matanzas, it's said the name recalls the matanza (massacre) of a group of Spaniards during an early indigenous uprising. In 1628 the Dutch pirate Piet Heyn captured a Spanish treasure fleet carrying 12 million gold florins in the Bay of Matanzas, ushering in a lengthy era of smuggling and piracy. Undeterred by the pirate threat, 30 families from the Canary Islands arrived in 1693, on the orders of King Carlos III of Spain, to found the town of San Carlos y Severino de Matanzas; the first fort went up in 1734. In 1898 the bay saw the first engagement of the Spanish-American War.

In the late 18th and 19th centuries, Matanzas flourished through coffee exporting and the building of numerous sugar mills. In 1843, with the laying of the first railway to Havana, the floodgates for prosperity were opened. The second half of the 19th century became a golden age: the city set new cultural benchmarks with the development of a newspaper, a public library, a high school, a theater and a philharmonic society. Due to the large number of writers and intellectuals living in the area, Matanzas became known as the 'Athens of Cuba' with a cultural scene that dwarfed even Havana's.

It was then that African slaves, imported to meet burgeoning labor demands, began to foster another reputation for Matanzas – as the spiritual home of rumba. In tandem, and from the same roots, spread a network of Santería cabildos (associations) – brotherhoods of those from slave descent who came together to celebrate the traditions and rituals of their African ancestors. Both rumba and cabildos flourish in Matanzas to this day.

Other landmarks in Matanzas' history include staging Cuba's first danzón performance (1879); later the city produced nationally important poets Cintio Vitier and Carilda Oliver Labra.