Caused by the longstanding ideological tug-of-war of federalism versus centralism between the liberals, conservatives, and nationalists of Colombia following the implementation of the Constitution of 1886 and the political process known as the Regeneración, tensions ran high after the presidential election of 1898, and on 17 October 1899, official insurrection against the national government was announced by members of the Liberal Party in the Department of Santander.

Conservative and liberal factions of those two countries, as well as of Guatemala, El Salvador, and Nicaragua, backed their respective parties within Colombia.

With an estimated 100,000 to 180,000 fatalities, about 2.5–3.8 percent of the nation's population at that time, the conflict was the deadliest and most destructive civil war in the history of Colombia.

It led to severe economic, political, and social repercussions for the country, including a partial collapse of the nation's economy, continued governmental instability, and the eventual loss of the Department of Panama as an incorporated territory of the republic in 1903.

The Regeneración brought relative peace to Colombia, but ultimately failed to resolve the internal political and economic disputes between the disparate departments of the country.

On 17 October 1899, official insurrection against the National government was announced by members of the Liberal Party in the Department of Santander, and hostilities began in earnest on 11 November with the Battle of Bucaramanga.

However, due to the imprudence of some of the Liberal generals, especially Paolo Emilio Villar,[4] who wished to begin the war on October 17, it was changed.

The first peace treaty, which formalized the cessation of hostilities, was signed on the plantation Neerlandia on October 24, 1902; the fighting had ended by the mid-point of that year in Panama.

From late 1901, fighting occurred between the ships Admiral Padilla (Liberal) and the Lautaro (Chilean property, lent to the conservatives), which was defeated by the former in front of the City of Panama on January 20, 1902.

Later the threat was from the American navy, sent by the government of Theodore Roosevelt to protect the United States' future interests in the construction of the Panama Canal.