Eugenides was born in Detroit, Michigan to a father of Greek descent and a mother of English and Irish ancestry. Eugenides is the youngest of three sons. He attended Grosse Pointe's private University Liggett School and then Brown University (where he became friends with contemporary Rick Moody). He graduated from Brown in 1982 after taking a year off to travel across Europe and volunteer with Mother Teresa in Calcutta, India. Of his decision to study at Brown, Eugenides remarked "I chose Brown largely in order to study with John Hawkes, whose work I admired. I entered the honors program in English, which forced me to study the entire English tradition, beginning with Beowulf. I felt that since I was going to try to add to the tradition, I had better know something about it." In 1986, he earned an M.A. in English and Creative Writing from Stanford University.
Eugenides knew he wanted to be a writer from a relatively early age, stating "I decided very early; during my junior year of high school. We read A Portrait of the Artist as a Young Man that year, and it had a big effect on me, for reasons that seem quite amusing to me now. I'm half Irish and half Greek—my mother's family were Kentuckians, Southern hillbillies, and my paternal grandparents immigrants from Asia Minor—and, for that reason, I identified with Stephen Dedalus. Like me, he was bookish, good at academics, and possessed an "absurd name, an ancient Greek." [...] I do remember thinking [...] that to be a writer was the best thing a person could be. It seemed to promise maximum alertness to life. It seemed holy to me, and almost religious." Of his earliest literary influences, Eugenides has cited "[...] the great modernists. Joyce, Proust, Faulkner. From these I went on to discover Musil, Woolf, and others, and soon my friends and I were reading Pynchon and John Barth. My generation grew up backward. We were weaned on experimental writing before ever reading much of the nineteenth-century literature the modernists and postmodernists were reacting against."
Eugenides was raised in Detroit, Michigan and cites the influence of the city and his high-school experiences on his writings. He has said that he has "a perverse love" of his birthplace. "I think most of the major elements of American history are exemplified in Detroit, from the triumph of the automobile and the assembly line to the blight of racism, not to mention the music, Motown, the MC5, house, techno." He also says he has been haunted by the decline of Detroit.

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