He was educated at Tavistock Grammar School before joining his father's newsagent and book business in 1846, at which time the firm became W H Smith & Son.

It has been claimed that Smith's appointment was the inspiration for the character of Sir Joseph Porter, KCB, in Gilbert and Sullivan's 1878 comic opera, H.M.S.

Gilbert had written to Sullivan in December 1877, "The fact that the First Lord in the opera is a Radical of the most pronounced type will do away with any suspicion that W. H. Smith is intended".

In 1885, a redistribution of seats led to Smith now standing for the Strand division in Westminster, and he served as Chief Secretary for Ireland for a short period the following year.

He died shortly afterwards at Walmer Castle, Kent, and his widow was created Viscountess Hambleden in his honour and took the title from the village close to the Smiths' country house of Greenlands, near Henley-on-Thames, Oxon.