Barton was born in Gravesend and was educated at Imperial College, London, where he obtained his PhD in 1942. After doing some industrial research he spent a year as visiting lecturer at Harvard before being appointed reader (1950) and then professor (1953) in organic chemistry at Birkbeck College, London. Barton moved to a similar chair at Glasgow University in 1955 but returned to Imperial College in 1957 and held the chair of chemistry until 1978, when he became director of the Institute for the Chemistry of Natural Substances at Gif-sur-Yvette in France. In 1986 he became a distinguished professor at Texas Agricultural and Mechanical University.

In 1950 Barton published a fundamental paper on conformational analysis in which he proposed that the orientations in space of functional groups affect the rates of reaction in isomers. Barton discussed six-membered organic rings, particularly, following the earlier work of Odd Hassell, the ‘chair’ conformation of cyclohexane and explained its distinctive stability.

This was done in terms of the distinction between equatorial conformations, in which the hydrogen atoms lie in the same plane as the carbon ring, and axial, where they are perpendicular to the ring. He confirmed these notions with further work on the stability and reactivity of steroids and terpenes.

It was for this work that he shared the 1969 Nobel Prize for chemistry with Hassell. Barton's later work on oxyradicals and his predictions about their behavior in reactions helped in the development of a simple method for synthesizing the hormone aldosterone.