Formed in Mazatlán, Sinaloa, in 2010 by Edén Muñoz, the band has had several lineup changes, with the current roster consisting of lead vocalist Beto Gastélum, backing vocalist & twelve-string guitarist Tony Elizondo, diatonic accordionist Martín "Trompudo" López, sousaphonist Alejandro Gaxiola, and drummer Erick García.

Their first nationwide hit was "El tierno se fue" ("The nice guy is gone") in 2011, a ranchera written by Lalo Ayala which contains many innuendos and describes a sexual act in detail.

In January 2014, drummer Augusto Guido left the band to work on his own group, "Los de Sinaloa"; he was replaced by Erick García.

[5] In March 2017, Calibre 50 made history when the band became the first Regional Mexican act to perform on the Conan show on an episode that took place in Mexico City.

On April 26, 2018, Calibre 50, along with Colombian Urban singer J Balvin, received an award from Pandora Radio for being the first artists to surpass a billion streams on the platform.

[10] On April 1, 2023, guitarist and backing vocalist Armando Ramos left Calibre 50 after 13 years to start his own band, "Al Tiro".

The very next day, on April 2, 2023, accordionist and backing vocalist Ángel Saucedo left Calibre 50 after only one year to begin a solo career.