Most studied classics at Harvard from 1968 on and received a B.A. Summa Cum Laude in Classics (Latin) in 1972. He then took a Masters course at Corpus Christi College at Oxford University until 1973, when he continued at the Department of Comparative Literature of Yale University, receiving a M. Phil. in 1978. Two years later, he received a Ph.D. under Paul de Man with a thesis called "The Bait of Falsehood: Studies in the Rhetorical Strategy of Poetic Truth in the Romantic Period". Simultaneously, from 1976 to 1978, he studied classics at the Philologisches Seminar of Eberhard Karls Universität Tübingen and was awarded D.Phil. under Richard Kannicht with a thesis entitled "Pindar's Truth: Unity and Occasionality in the Epinician Ode".
Most’s work ranges from Greek to Latin authors, from literature to philosophy, and from history and methodology of classical studies to modern literary theory and reception history. In particular, he studies the relationship of the modern towards the ancient world, including New Testament topics such as the story of Doubting Thomas.