Born in Tasmania, Australia, Derwent Lees moved to London in 1905 and studied at the Slade School of Fine Art with Henry Tonks and Frederick Brown. After completing his studies, he stayed on to teach for a decade, working on and off whilst his artistic career took off, with works exhibited at the Goupil Galleries and the Chenil Gallery, Chelsea, in 1914.

Between 1910 and 1912, Lees spent most of his time painting with artists and friends Augustus John, Ambrose McEvoy, and James Dickson Innes in North Wales and Spain. During the winter months, they would go to Collioure, a small fishing village on the Mediterranean in the south of France, a hub for artists in the early twentieth century, popular with Picasso, Matisse, Derain, and Braque. There, Lees was the only Australian artist introduced to Fauvism, subsequently completing a series of vivid landscapes. Some of his works from this time can now be found in the Tate Gallery, London.

In 1913, Lees married Edith, known at Lyndra, who frequently modelled for John but then became the subject in Lee's own works. Specifically, she featured in a series of works completed in Aldbourne, Wilshire, which depict her amongst nature. In the same year, three of his paintings exhibited internationally as the only Australian artist represented at The Armory Show, which sold out in New York, Chicago, and Boston.

His artistic career was cut short due to mental health problems, which sent him to hospital in Surrey until his death in 1931. But this did not limit the success of his works. During this time, the Redfern gallery held a retrospective exhibition, with Leeds and Manchester Galleries purchasing his works.

Currently, his works are owned by many public collections, including the National Gallery Australia, The Glynn Vivian Art Gallery in Wales, and the National Gallery of Victoria in Melbourne.