Robert Main attended school in Portsea, Portsmouth before studying mathematics at Queens' College, Cambridge, where he graduated as sixth wrangler in 1834.
In 1860 he became director of Radcliffe Observatory at Oxford University after the death of Manuel Johnson, and was elected as a Fellow of the Royal Society.
Main completed the questionnaire on which Francis Galton based his English Men of Science (1874), and his recorded answers included the following comments: Main supervised the third (1859) edition of Sir John Herschel's A Manual of Scientific Enquiry, prepared for the use of Her Majesty's Navy and adapted for travellers in general (1849), which included an article on geology by Charles Darwin.
He also published observations made of rainfall in Oxford over 25 years from 1851 to 1875, and contributed to the Fortnightly Review during the editorship of G. H. Lewes.
His other works include the annual address for 1875 to the Philosophical Society at the Victoria Institute (entitled Modern Philosophic Scepticism Examined) and a sermon on I Corinthians 1:22-24 given to the British Association for the Advancement of Science in the same year.