Blythe graduated from Monticello High School in 1987 and the Crane School of Music at the State University of New York at Potsdam in 1992. She was the recipient of the prestigious Richard Tucker Award in 1999. SUNY Potsdam awarded her the degree of Doctor of Music honoris causa in 2006.
In 1996, Blythe's career was transformed, standing in for Marilyn Horne at the Metropolitan opera as Mistress Quickly in "Falstaff." Her breakthrough performance came three years later when she sang Cornelia in Handel's Giulio Cesare.