In 1953 he received a PhD from the California Institute of Technology; the German-born Wilson Observatory-based astronomer Walter Baade was his advisor.

In 1952 Baade surprised his fellow astronomers by announcing (at the 1952 Conference of the International Astronomical Union, in Rome) his determination of two separate populations of Cepheid variable stars in the Andromeda Galaxy, resulted in a doubling of the estimated age of the universe (from 1.8 to 3.6 billion years).

Hubble had posited the earlier value; he had considered only the weaker Population II Cepheid variables as standard candles.

Sandage performed photometric studies of globular clusters, and calculated their age to be at least 25 billion years.

The current cosmological estimates of the age of the universe, in contrast, are typically of the order of 14 billion years.

As part of his studies concerning the formation of galaxies in the early universe, he co-wrote the paper[6] now referred to as ELS after the authors Olin J. Eggen, Donald Lynden-Bell and Sandage, first describing the collapse of a proto-galactic gas cloud into our present Milky Way Galaxy.

In 1962 Sandage studied the possibility of directly measuring the temporal variation of the redshift of extra-galactic sources.