Its capital Artigas comes at the end of the "Guerra Grande" in order to consolidate the borders with Brazil, with the name of San Eugenio del Cuareim.

A city named Santa Rosa del Cuareim, now known as Bella Unión, was founded by Fructuoso Rivera and Guarani refugees after the Eastern Missions campaign against Brazil in 1829 (see: Thirty-Three Orientals).

In 1929, the national government to mark the centenary of the campaign of Missions, sent a bill to the Senate, which established the name Bella Unión, which for that time was a villa.

Two portions of the department's border with Brazil are disputed (Isla Brasilera or Brazilian Island near Bella Unión, and an area called Rincón de Artigas near Masoller), but unlike many border disputes between Latin American countries, this issue has not strained Uruguay's relations with Brazil, which remain friendly.

Semi-precious gemstones, such as agates and amethysts, are also found in the department, and an entire industry has risen up around their extraction and manufacturing, especially near the capital city of Artigas.

[1] The proximity of the department to Brazil has made it possible for an important flow of trade to be established here, but unfortunately this is generally unfavorable to Uruguayan economic interests.