He was appointed Lecturer, Royal College of Science (1872) and assisted Norman Lockyer with spectroscopy.

Meldola was in charge of the British Eclipse Expedition to the Nicobar Islands (1875) and was Professor of Chemistry, Technical College, Finsbury (1885).

He was elected Fellow of the Royal Society in 1886 (Charles Darwin was one of his proposers), awarded the Davy Medal in 1913, and was Vice-President of the Council from 1914–1915.

Meldola was a keen naturalist, spending five years eagerly collecting evidence on mimicry in butterflies, inspired by Charles Darwin's On the Origin of Species.

His work provided evidence for natural selection, acknowledged by the evolutionary zoologist Edward Bagnall Poulton in his book The Colours of Animals and thanked by Darwin for information on hexadactyly (a rare case of a person having six digits on each limb).