Spanish Governor Diego Velázquez founded a settlement here on July 25, 1515. The province covers 2,382 square miles (610 square kilometers) and is bordered by the Caribbean Sea and the Sierra Maestra Mountains, which contain the highest point in Cuba at 6,476 ft. (1,974 m). Santiago is Cuba's second largest city and has an eclectic collection of architectural styles, ranging from colonial to art deco. The city center is packed with beautiful pastel colored buildings, many in better condition than those found in the capital.

During the 17th century, Santiago was besieged by pirates from both France and England. This led to the construction of the Castillo del Morro, which is still intact today, and houses a museum about the region's maritime history. Because of its location, Santiago has received many waves of immigrants; it was the first city in Cuba where African slaves were brought. Later, many French landowners fled to the city from the slave uprisings in Haiti during the 18th century. Jamaicans have also migrated to Santiago in significant numbers. The Moncada barracks, just outside Santiago, were the sight of the first attack by Castro and his forces on July 26, 1953. The attack failed, but Santiago is still known as the Ciudad Héroe (the City of Heroes).

The city is centered around Céspedes Park. Surrounding it are many of Santiago's most important buildings, including the Cathedral, the Museo de Ambiente Histórico Cubano (Museum of Cuban History), the Palacio de Gobierno, and the former home of Diego Velázquez. Other places of interest include the Museo 26 de Julio, commemorating the Moncada attacks, the Museo de la Lucha Clandestina (Museum of the Underground Movement), and the Museo Bacardi. Take the time to stroll down charming streets such as Calle Heredia and Calle Padre Pico.

The most popular pilgrimage site in Cuba is the Santuario Nacional a Nuestra Senora de la Caridad del Cobre. An impressive altar is housed in a church with dual bell towers that stands alone on a hill about 15 kilometers northwest of of the city center.

Some sights east of Santiago include the Granjita Siboney, Valle de la Prehistoria (Prehistoric Valley), and the Acuario de Baconao (Baconao Aquarium). Granjita Siboney is a famous revolutionary hideout. The Valle de la Prehistoria is a park with lifelike concrete replicas of dinosaurs. The Acuario de Baconao is an aquarium that presents dolphin and sea lion shows and offers places to watch sharks and dolphins from a tunnel underneath the pool. There is also a small marine museum.