He is known for his realistic depictions of rural, small-town life in the Northeastern United States, particularly in Maine, Pennsylvania, and Russo's native Upstate New York.

[2] The subject of his doctoral dissertation was the works of the early American writer, historian and editor Charles Brockden Brown.

Much of his work is semi-autobiographical, drawing on his life from his upbringing in upstate New York to his time teaching literature at Colby College, where he retired from in 1996 to pursue writing full-time.

Besides his work as a book author, Russo along with director Robert Benton co-wrote the 1998 film Twilight, starring Paul Newman.

Russo's 1997 novel Straight Man was adapted by Paul Lieberstein and Aaron Zelman into a television show entitled Lucky Hank starring Bob Odenkirk for AMC.