Born in Washington DC, Davis was educated at the universities of Maryland and Yale where he obtained his PhD in 1942. After serving four years in the USAAF, Davis took the post of senior chemist at the Brookhaven National Lab, New York, and remained there until his retirement in 1984. He has continued to work, however, as a research professor in the astronomy department of the University of Pennsylvania, Philadelphia.

For many years Davis, an experimentalist, worked on the detection of neutrinos emitted by the Sun. In working out the reactions that power the Sun, theorists, such as John Bahcall, predict that a certain number of neutrinos should be produced, and that a measurable number should be detectable on Earth.

The problem is that neutrinos have a very low probability of interaction with matter. Millions of them pass unimpeded through the Earth every second. The average time lapse for an interaction of a neutrino with an atom is 10³⁶ seconds. To increase the probability of detecting a neutrino it was necessary to use a detector containing a large number of atoms. The result was a 100,000-gallon tank of cleaning fluid (tetrachloroethene), containing about 10³⁰ atoms. To exclude confusing interactions with cosmic rays Davis deposited his tank in 1969 at the bottom of the one-mile-deep Homestake Mine at Lead, South Dakota.

Davis was looking for a specific reaction. Neutrinos can react with the isotope chlorine-37 (about a quarter of chlorine atoms) converting it into the radioactive argon-37. The argon atoms could be removed at regular intervals and counted. Theory predicted that Davis should observe 7.9±2.6 solar neutrinos per second, otherwise known as solar neutrino units (SNUs). Actually Davis began by observing about 2 SNUs, and after twenty years of continuous observation he is still observing no more than 2 SNUs.

Davis sought to eliminate the possibility that the anomalous results are the products of a faulty experimental design. After twenty years spent refining his work, he remained convinced that any errors were unlikely to be traced to the experiment. Further, other workers have produced very similar results. This discrepancy between theory and experiment constitutes the solar neutrino problem.