William Hume-Rothery was born in Surrey on 15 May 1899. He obtained a scholarship at Cheltenham College in 1912. In 1916 he took the army entrance examination, achieving fifth place, and passed into the Royal Military Academy in Woolwich. However, in the following year he contacted cerebrospinal meningitis. Nerve damage left him completely deaf.

In 1918 Hume-Rothery entered Magdalen College, Oxford, and obtained a first class Honours degree in chemistry. After graduation he joined the Royal School of Mines, where he researched intermetallic compounds. In 1925 he was awarded a Ph.D.

Hume-Rothery returned to Oxford in 1925 and was elected to a Senior Demyship at his old college. There he carried on research in intermetallic compounds and problems on the borderline of metallography and chemistry. When his Demyship terminated in 1929 he continued his work in Oxford with an Armourers & Braziers Research Fellowship in Metallurgy, a position he held until 1932. In 1932 he was elected to a Warren Research Fellowship of the Royal Society, a position he held until 1955.

In 1955 Hume-Rothery was appointed George Kelly Reader in Metallurgy at Oxford University. In 1958 he was elected to the Isaac Wolfson Chair of Metallurgy, and to a Professorial Fellowship, St. Edmund Hall, Oxford, positions he held until his retirement in 1966. From 1965 until his death in 1968 he also served as a consultant to the Atomic Energy Research Establishment (A.E.R.E.) at Harwell.

Hume-Rothery was elected a Fellow of the Royal Society in 1937. He was appointed O.B.E. in 1951.