He read law at Girton College, Cambridge, preferring it over English because "literature was too precious" and he wanted it to remain a hobby.

O'Neill then entered full-time practice as a barrister in London, principally in the field of business law.

He is best known for Netherland, which was published in May 2008 and was featured on the cover of the New York Times Book Review, where it was called "the wittiest, angriest, most exacting and most desolate work of fiction we've yet had about life in New York and London after the World Trade Center fell".

[8] Literary critic James Wood called it "one of the most remarkable postcolonial books I have ever read".

In an interview with the BBC in June 2009, US President Barack Obama revealed that he was reading it, describing it as "an excellent novel.

[18] O'Neill is also the author of Good Trouble (2018), a collection of short stories, most of which first appeared in the New Yorker or Harper's magazine.