On May 10, 1919, Mitscher was among a group of naval aviators attempting the first transatlantic crossing by air. Among the men involved was future admirals Jack Towers and Patrick N. L. Bellinger. Mitscher piloted NC-1 under the command of Bellinger, one of three Curtiss NC flying boats that attempted the flight. Taking off from Newfoundland, he nearly reached the Azores before heavy fog caused loss of the horizon, making flying in the early aircraft extremely dangerous. What appeared to be fairly calm seas at altitude turned out to be a heavy chop, and a control cable snapped while setting the aircraft down. Mitscher and his five crewmen were left to sit atop the upper wing of their "Nancy" while they waited to be rescued. Of the three aircraft making the attempt, only NC-4 successfully completed the crossing. For his part in the effort Mitscher received the Navy Cross, the citation reading:
Mitscher was also made an officer of the Order of the Tower and Sword by the Portuguese government on June 3, 1919.
On October 14, 1919, Mitscher reported for duty aboard Aroostook, a minelayer refitted as an "aircraft tender" that had been used as a support ship for the "Nancys" transatlantic flight. He served under Captain Henry C. Mustin, another pioneering naval aviator. Aroostook was assigned temporary duties as flagship for the Air Detachment, Pacific Fleet. Mitscher was promoted to commander on July 1, 1921. In May 1922, he was detached from Air Squadrons, Pacific Fleet (San Diego, California) to command Naval Air Station Anacostia, D.C.