During the First World War he joined the West Riding Regiment, and later transferred to the Royal Engineers.
After returning from active service in World War I, Appleton became assistant demonstrator in experimental physics at the Cavendish Laboratory in 1920. He was professor of physics at King's College London (1924–36) and professor of natural philosophy at Cambridge University (1936–39). From 1939 to 1949 he was secretary of the Department of Scientific and Industrial Research. Knighted in 1941, he received the 1947 Nobel Prize in Physics for his contributions to the knowledge of the ionosphere, which led to the development of radar.
In 1902 Oliver Heaviside and Arthur Edwin Kennelly independently proposed the idea of there being a conducting layer that reflected radio signals. Guglielmo Marconi had been able to make his historic transatlantic transmissions; to achieve this, refraction of the signals was necessary to reach its destination.
In his work, Appleton had observed that the strength of the radio signal from a transmitter on a frequency such as the medium wave band and over a path of a hundred miles or so was constant during the day but that it varied during the night. This led to him to believe that it was possible that two radio signals were being received. One was traveling along the ground, and another was reflected by a layer in the upper atmosphere. The fading or variation in strength of the overall radio signal received resulted from the interference pattern of the two signals.
To prove his theory, in 1924 Appleton used the British Broadcasting Corporation (BBC) radio broadcast transmitter at Bournemouth, England. This transmitted a signal towards the upper reaches of the atmosphere. He received the radio signals near Cambridge, proving they were being reflected. By making a periodic change to the frequency of the broadcast radio signal he was able to measure the time taken for the signals to travel to the layers in the upper atmosphere and back. In this way he was able to calculate that the height of the reflecting layer was 60 miles above the ground.
From 1949 until his death in 1965, he was Principal and Vice-Chancellor of the University of Edinburgh.
In 1974 the Radio and Space Research Station was renamed the Appleton Laboratory in honour of the man who had done so much to establish the UK as a leading force in ionospheric research, and had been involved with the station first as a researcher and then as secretary of its parent body, the Department of Scientific and Industrial Research.