Leslie was born into an artistic family, his father was the notable genre painter Charles Robert Leslie RA, and his uncle Robert Leslie was a marine artist. He studied art first at Carys Art Academy, then from 1854 at the Royal Academy. His first exhibition at the Academy was in 1859, and he showed his work every year thereafter. He became an Associate (ARA) in 1868 and a full Royal Academician (RA) in 1876.
George Dunlop Leslie lived early on in St Johns Wood (London), and was part of the St Johns Wood Clique, a group of artists who favoured light-hearted genre subjects. From 1884–1901 he was resident at "Riverside", St. Leonards Lane, Wallingford, Oxfordshire. His sister Mary Leslie (1833–1907), also an artist, lived at "Cromwell Lodge" next door. Fellow artist, James Hayllar, was also a resident of the village and they painted a portrait of Queen Victoria together for her Golden Jubilee in 1887. From 1906 he lived at "Compton House" in Lindfield, Sussex.