Based in Pearl Harbor from 27 January 1941, Colorado operated in the Hawaiian training area in intensive exercises and war games until 25 June, when she departed for the west coast and overhaul at Puget Sound Navy Yard which lasted until 31 March 1942. Two of the original 12 5 in (130 mm)/51 cal guns were removed during overhaul, and the 5 in (130 mm)/25 cal guns were replaced by an equal number of 5 in (130 mm)/38 cal guns. On 31 May, Colorado and Maryland set sail from the Golden Gate to form a line of defense against any Japanese attack mounted on San Francisco.
After west coast training, Colorado returned to Pearl Harbor on 14 August to complete her preparations for action. She operated in the vicinity of the Fiji Islands and New Hebrides from 8 November-17 September 1943 to prevent further Japanese expansion. She sortied from Pearl Harbor on 21 October to provide preinvasion bombardment and fire support for the invasion of Tarawa, returning to port on 7 December. After west coast overhaul, Colorado returned to Lahaina Roads, Hawaiian Islands, on 21 January 1944 and sortied the next day for the Marshall Islands operation, providing preinvasion bombardment and fire support for the invasions of Kwajalein and Eniwetok until 23 February, when she headed for Puget Sound Navy Yard and overhaul.

Joining other units bound for the Mariana Islands operation at San Francisco, Colorado sailed on 5 May by way of Pearl Harbor and Kwajalein for preinvasion bombardment and fire support duties at Saipan, Guam, and Tinian from 14 June. On 24 July, during the shelling of Tinian, Colorado received 22 shell hits from shore batteries but continued to support the invading troops until 3 August. After repairs on the west coast, Colorado arrived in Leyte Gulf on 20 November 1944 to support American troops fighting ashore. A week later she was hit by two kamikazes which killed 19 of her men, wounded 72, and caused moderate damage. Nevertheless as planned, she bombarded Mindoro from 12-17 December before proceeding to Manus Island for emergency repairs.

Returning to Luzon on 1 January 1945, she participated in the preinvasion bombardments in Lingayen Gulf. On 9 January, accidental gunfire hit her superstructure killing 18 and wounding 51. After replenishing at Ulithi, Colorado joined the preinvasion bombardment group at Kerama Retto on 25 March for the invasion of Okinawa. She remained there supplying fire support until 22 May, when she cleared for Leyte Gulf.

Returning to occupied Okinawa on 6 August, Colorado sailed from there for the occupation of Japan, covering the airborne landings at Atsugi Airfield, Tokyo on 27 August. Departing Tokyo Bay on 20 September, she arrived at San Francisco on 15 October, then steamed to Seattle, Washington, for the Navy-Day celebration on 27 October. Assigned to Operation Magic Carpet duty, she made three runs to Pearl Harbor to transport 6,357 veterans home before reporting to Bremerton Navy Yard for inactivation. She was placed out of commission in reserve there on 7 January 1947, and sold for scrapping on 23 July 1959.