The Gamma saw fairly limited civilian service as mail planes with Trans World Airlines but had an illustrious career as a flying laboratory and record-breaking aircraft.

[1] Twenty Five Gamma 2Es were assembled in China from components provided by Northrop; these were deployed in various attack missions during the early stages of the Second Sino-Japanese War, particular against Imperial Japanese naval assets.

In 1935, Howard Hughes improved on this time in a modified Gamma 2G leased from Jacqueline Cochran, making the west-east transcontinental run in 9 hours, 26 minutes, and 10 seconds.

On November 23, 1935, Ellsworth and Canadian pilot Herbert Hollick-Kenyon attempted the world's first trans-Antarctic flight from Dundee Island in the Weddell Sea to Little America.

The intrepid crew took six days to travel the remainder of the journey and stayed in the abandoned Richard E. Byrd camp until being found by the Discovery II research vessel on January 15, 1936.