After Southgate County Grammar School, in 1963 Holford-Strevens went up to Christ Church, Oxford, to read Literae Humaniores (a form of classical studies), and stayed on to obtain his doctorate there with a dissertation entitled Select Commentary on Aulus Gellius, Book 2 (1971).
In 1971 Holford-Strevens started work with the Oxford University Press as a graduate proof reader and later rose to become consultant scholar-editor there. His first book-length publication, Aulus Gellius, was published in 1988. Gellius was a Roman judge who corresponded with or knew many of the major figures of his time, including Favorinus, Fronto, Apuleius, and Herodes Atticus. His work Attic Nights was a miscellany of learning that ranged over several fields. Holford-Strevens's book was hailed by Hugh Lloyd-Jones as a masterpiece characterized by a "sharp critical intelligence". In appraising the remarkable quality of his classical scholarship, Lloyd-Jones stated that Holford-Strevens was one of the most learned men in England, comparing him to Sebastiano Timpanaro, who also managed to combine a career in a publishing house with world-class contributions to scholarship. His prodigious erudition is widely acknowledged. W. H. Auden once called on dons entertaining him in Oxford to stop chatting, explaining that he wished to listen to Holford-Strevens's conversation as he held forth in another corner of the room.
Numerous anecdotes circulate concerning his mannerisms, from his being barred from a college dining room on account of what were called his "mediaeval eating manners" to his ability to navigate streets while buried in The Times, and yet managing to miss running into lampposts.
By the time of his retirement in 2011, Holford-Strevens had proof-read or edited over 500 books, and in retirement he is still active and is working on a new commentary on Gellius. He lives in St Bernard's Road, Oxford.
His work as a copy-editor was recognized in 2016 by the award of the British Academy President's Medal for outstanding service to the cause of the humanities and social sciences.