As victory over Spain became increasingly apparent, leaders from present-day Venezuela, Colombia, and Panana convened a congress in February 1819 in Angostura (present-day Ciudad Bolívar, Venezuela) and agreed to unite in a republic to be known as Gran Colombia. After Bolívar was ratified as president in August 1819, he left Santander, his vice president, in charge of Gran Colombia and traveled south to liberate present-day Ecuador, Peru, and Bolivia. When present-day Ecuador was liberated in 1822, it also joined Gran Colombia. In 1821 the Cúcuta Congress wrote a constitution for the new republic. The Cúcuta political arrangement was highly centralized and provided for a government based on popular representation with a bicameral Congress, a president, and a Supreme Court consisting of five magistrates. The constitution also guaranteed freedom for the children of slaves; freedom of the press; the inviolability of homes, persons, and correspondence; the codification of taxes; protectionist policies toward industry and agriculture; and the abolition of the mita system of labor.

Nonetheless, political rivalries and regional jealousies progressively weakened the authority of the new central state. Venezuelan leaders especially were resentful of being ruled by Santander, a native of present-day Colombia, in the absence of their president and fellow Venezuelan, Bolívar. In 1826 General José Antonio Páez led a Venezuelan revolt against Gran Colombia. Outbreaks and disturbances also occurred elsewhere.