Educated at St Paul's School, Hammersmith, he went to Balliol College, Oxford, but failed to complete his degree through ill-health after two years.

His first work was as a stage-set designer, notably for J. M. Barrie's The Adored One and George Bernard Shaw's Pygmalion (1914).

The need to support his young family led Mackail to write fiction at a time when office jobs became insecure after the end of the war.

A. Milne and the dedication to the UK edition of Wodehouse's Summer Lightning reads "To Denis Mackail, author of 'Greenery Street', 'The Flower Show' and other books which I wish I had written".

After a nervous breakdown, Mackail, as therapy, set about writing the official biography of J. M. Barrie, which appeared in 1941.