His research on metallic cerium, which he together with Thomas Norton obtained first in 1872, started his academic career.

That year he was sent to Denver to establish a chemical laboratory for the Rocky Mountain Division of the Survey.

During an analysis of the uranium containing mineral uranite he discovered that a gas evolved.

A reexamination by Ramsay of Hillebrand's samples showed that the gas from uranite contained a large amount of nitrogen.

Hillebrand was elected to the American Philosophical Society in 1906 and the United States National Academy of Sciences in 1908.