The son of a gunsmith, Powell was born at Tonbridge, Kent, and educated at Cambridge University, where he obtained his PhD in 1927. He spent virtually his entire career at Bristol University where he became Wills Professor of Physics in 1948 and director of the Wills Physics Laboratory in 1964.

Under Powell Bristol became a leading center for the study of nuclear particles by means of photographic emulsions. In this technique an ionizing particle crossing a sensitive plate coated with grains of silver bromide leaves clear tracks of its passage. From the size and path of the track much information about the nature of the particle can be inferred. In 1947 Powell, in collaboration with Giuseppe Occhialini (1907–1993), published a standard work on the subject, Nuclear Physics in Photographs. It was this technique that allowed Powell to discover the pi-meson (or pion) in 1947 in the plates of cosmic rays. The existence of such a particle had been predicted in 1935 by Hideki Yukawa, and Powell's discovery thus went some way to establish a coherent picture of nuclear phenomena.

For his discovery Powell was awarded the 1950 Nobel Prize for physics.