Cherenkov came from a peasant family in Voronezh, Russia, and was educated at the university there, graduating in 1928. From 1930 he was a member of the Lebedev Institute of Physics in Moscow, serving there from 1953 as professor of experimental physics.

In 1934 Cherenkov was investigating the absorption of radioactive radiation by water when he noticed that the water was emitting an unusual blue light. At first he thought it was due simply to fluorescence but was forced to reject this idea when it became apparent that the blue radiation was independent of the composition of the liquid and depended only on the presence of fast-moving electrons passing through the medium.

It was later shown in 1937 by the Russian physicists Ilya Frank (1908–1990) and Igor Tamm (1895–1971) that the radiation was caused by electrons traveling through the water with a speed greater than that of light in water (though not of course greater than that of light in a vacuum). This Cherenkov radiation can be produced by other charged particles and can be used as a method of detecting elementary particles. Cherenkov, Frank, and Tamm shared the Nobel Prize for physics in 1958.