The First Mixed Brigade was established from the Fifth Regiment on 10 October 1936 in Alcalá de Henares as a result of the reorganization of the Spanish Republican Armed forces.

It would suffer many losses in the Battle of Brunete, including its Cuban brigade commander Alberto Sánchez, as well as a great number of officers and Chief of Staff Major Emilio Conejo.

In March 1937 the brigade took part with success in the Battle of Guadalajara and in April it was sent again to attack the Cerro de los Ángeles, ending again in failure.

On 24 August it took part in the Zaragoza Offensive attacking the Fuentes de Ebro sector in successive assaults without being able to make significant progress.

After conquering Teruel, the First Mixed Brigade was sent to a rearguard position together with the remainder of the 11th Division in order to recover following the heavy losses that had been inflicted on these units.

After conquering Móra d'Ebre, it arrived to the Pàndols Range defensive line and later it reached the Barranco de Santa Magdalena.

When the Francoist offensive against Catalonia began on 23 December 1938, the 1st Mixed Brigade was in the Garrigues area waiting to be reorganized, but it was sent to the Battle of the Segre front in order to plug a breach in the republican lines.

For a while it managed to stop the offensive of the Fascist Italian Corpo Truppe Volontarie near Les Borges Blanques, but by the beginning of January 1939 it had to retreat towards the north.