The name Guaqui is thought to derive from the song of a wading bird that lives in the waters of Titicaca, the wacana: its cry is similar to a wac, wac, wac.

Guaqui has been the setting of various historical events. A few kilometres away from the town centre, on June 20, 1811, the Argentine revolutionary troops of the First Assembly confronted the royalist troops of the Viceroyalty of Peru in a failed attempt to free these lands from the colonial yoke. A few years later, Mariscal Sucre passed through here on his triumphal march towards La Paz.

In recent times, thanks to the railway, Guaqui prospered and became one of Bolivia's main communication hubs. Today, the recovery and enhancement of this important historical heritage are clearly visible in its museum.