Scott grew up in Darien, Connecticut, where she was a volunteer emergency medical technician (EMT) with Post 53, a scout explorer post that serves as the town's volunteer ambulance service. One of her earliest pieces of writing was a nonfiction account of an EMT who lit fires, then helped rescue the victims. She became involved in the literary magazine for Darien High School.

She received her bachelor's degree from Trinity College in Hartford, Connecticut in 1983. Before graduating, she spent a year in an exchange program at Barnard College and helped edit its literary magazine. Before graduating college, she also worked as a copy editor for United Features Syndicate in New York and spent a year at the Elaine Johnson Literary Agency. There she was an assistant to Geri Thoma, who later became Scott's own agent.

Scott received her master's degree from Brown University in 1985 and taught creative writing there as well as at the University of Maryland and Princeton University. Since 1988 she has been in the English Department of the University of Rochester, where she has taught courses in creative writing, the contemporary novel, the writing of Charles Dickens and other subjects. She also sits on the contributing editorial board of the literary journal Conjunctions. In one of her graduate courses she's taught about the ways fiction corresponds to time. Translation for Scott is an issue of almost ultimate importance, as she herself has said and stated many times. Author and editor, Rebecca Housel, credits Scott's literary guidance during Housel's years as a student at the University of Rochester as being influential to Housel's later writing career.

She is married to James Longenbach, a poet, critic and fellow professor a the English Department. Like Scott, he is also a graduate of Trinity College (Class of 1981). They have two children.

For research, Scott has traveled as far as Austria and Alaska.