Until the Mexican-American War (1846 to 1849), the Pueblo area was controlled by Mexico, with all Catholic missions under the jurisdiction of the Archdiocese of Durango.

On November 15, 1941, Pope Pius XII separated territory from the Archdiocese of Denver to form the Diocese of Pueblo.

Pope John XXIII appointed Charles Buswell of the Diocese of Oklahoma City-Tulsa as the second bishop of Pueblo.

[3] That same year, Fernando Isern of the Archdiocese of Miami was appointed the fourth bishop of Pueblo by Pope Benedict XVI.

[8] After Isern retired in 2013, Pope Francis named Stephen Berg of the Diocese of Fort Worth to replace him.

Groves received four years probation and sex abuse treatment[10][11] In October 2006, the diocese paid a $4 million settlement to 23 male victims of Brother William Mueller, a Marianist band director at Roncalli High School in Pueblo between 1966 and 1971.

Yengich said that Maio, youth director for the diocese, would invite young boys to his residence, where he would ply them with alcohol and play strip poker with them.

[18] In December 2020, Weiser's final report revealed that there were an additional nine credibly accused clergy and 46 alleged victims in both the Diocese of Pueblo and Archdiocese of Denver.

[19][20] Four of these priests (Marvin Kapushion, Duane Repola, Carlos Trujillo, and Joseph Walsh) were accused of committing acts of sex abuse while serving in the Diocese of Pueblo.