Sittenfeld was born August 23, 1975, in Cincinnati, Ohio, the second of four children (three girls and a boy). Her mother, Elizabeth "Betsy" Curtis (Bascom), is an art history teacher and librarian at Seven Hills School, a private school in Cincinnati, and her father, Paul George Sittenfeld, is an investment adviser. Her younger brother, P. G. Sittenfeld, is a member of the Cincinnati City Council. She is of "half-Catholic, half-Jewish" background.
She attended Seven Hills School through the eighth grade, then attended high school at Groton School, a boarding school in Groton, Massachusetts, graduating in 1993. In 1992, the summer before her senior year, she won Seventeen magazine's fiction contest.
She attended Vassar College in Poughkeepsie, New York before transferring to Stanford University in Palo Alto, California. At Stanford, she studied creative writing, wrote articles for the college newspaper, and edited that paper's weekly arts magazine. At the time, she was also chosen as one of Glamourʼs College Women of the Year. She went on to earn an MFA from the Iowa Writers' Workshop at the University of Iowa.