Born in Eugene, Oregon, Applegate grew up in Clackamas, Oregon graduating from Clackamas High School in 1985. She graduated summa cum laude from Amherst College in 1989 and earned a Ph.D. in American Studies from Yale University in 1998.

Applegate has taught American History at Yale and Wesleyan University, and master classes on writing biography and memoir at Marymount Manhattan College in New York. Her work has appeared in the New York Times, the Los Angeles Times, the Chicago Tribune, the Boston Globe and the Wall Street Journal among other publications. She serves as a trustee on the governing boards of The New Haven Review, the Harriet Beecher Stowe House, the Yale Summer Cabaret, and the Friends of the Amherst College Library. She served as interim president of Biographers International Organization (BIO), a professional association for biographers.

Applegate is married to Bruce Tulgan, an expert on generational change in the workplace and the author of It's OK To Be The Boss.