The Granadine Confederation, created a few years earlier in 1858 by Mariano Ospina Rodríguez, was defeated in the capital Bogotá, with Mosquera deposing the newly elected president Bartolomé Calvo on July 18, 1861.

In the years prior to the outbreak of civil war, the central government under Mariano Ospina Rodríguez had attempted to thwart growing Liberal movements by supporting counter-insurrections in the member states.

The following day, Mosquera ordered the execution of a number of politicians and officials from the Confederacy, including Plácido Morales, Andrés Aguilar and Ambrosio Hernández.

Following the collapse of the Confederacy government and the assumption of power by Mosquera, a number of renegade generals in command of the remaining Confederate forces continued to resist, including Julio Arboleda in the Cauca, General Braulio Henao in Antioquia and General Leonardo Canal in Santander, however with the assassination of the first on November 12, 1862, the defeat of Henao at the battle of Santa Barbara, and the capitulation of Canal in Pasto, Nariño, resistance to Mosquera's new government was relatively short lived, and on May 8, 1863, the United States of Colombia was officially created from the Rionegro Convention.

[7] The new government also clashed with the positions of the church when, to help rejuvenate an economy ravaged by civil war, was put under secular control with its lands being sold to industrialists and developers.