The settlement was a fortified port which had to be moved on three occasions because it was constantly attacked by Carib natives and European rivals, such as the Dutch and English.

[6] In 1576 Saint Thomas of Guyana was first located in present-day Ciudad Guayana by missionaries near the Caroní River until Dutch forces led by Captain Adrian Janson destroyed the town in 1579.

[6] The second settlement was founded by Don Antonio de Berrío in 1595, who had arrived from the New Granada with the mission of colonizing Guiana, and was moved westward down the Carońi about 66 kilometres (41 mi).

[6][7] Fernando de Berrio was present on March 11, 1619 in the destroyed Saint Thomas of Guyana with the credentials granted by the Royal Audience of Santa Fe, just a few months after the decapitation of Raleigh in 1618.

In 1629, English and Dutch pirates, under the command of Adrian Jansz Pater, attacked and destroyed Saint Thomas of Guyana and afterwards fortified themselves in the branches and creeks of the Orinoco River.

In 1637 the Dutch, settled at the mouths of the Amakura, Essequibo and Berbice, again attacked and burned Saint Thomas of Guyana and raided Trinidad.

The Jesús Soto Museum of Modern Art, named in his honor and designed by Venezuelan architect Carlos Raúl Villanueva, was opened in 1973.

[16] Universidad Nacional Experimental de Guayana (UNEG) is another public institution in Ciudad Bolívar, founded 9 March 1982 by resolution N° 1.432 of President Luis Herrera Campins.

Ciudad Bolívar's historic district is a popular tourist attraction, featuring houses and buildings that date from the colonial period.

Ciudad Bolívar is also the birthplace of musicians Antonio Lauro, Cheo Hurtado, Iván Pérez Rossi, and the home of the musical group Serenata Guayanesa.

Traditional local cuisine includes desserts and preserves made of cashew nuts, eaten alone or roasted with salt.