Jane's earliest years were spent in the city of Milwaukee, Wisconsin, where her mother, Evelyn, a dedicated schoolteacher, and her father, Edward, a former Defense Department employee, raised her alongside her three younger siblings. Her brothers, Jim and Bill, followed different paths, with Jim becoming a teacher and Bill an entrepreneur, while her sister, Mary, found employment with an Internet company.
Jane's academic pursuits led her to the University of Wisconsin, where she majored in theater and forged a close bond with Tony Shalhoub, who encouraged her to pursue a career in acting. Sheeding the advice of her friend, Jane enrolled at Yale University and joined the Yale Repertory Company, where she gained valuable experience and recognition for her performances.
Notable successes in both film and theater followed, including positive reviews for her replacement of Mercedes Ruehl in Neil Simon's Broadway play, "Lost In Yonkers". Jane's time at Yale also brought her into contact with her future roommate, Kate Burton, the daughter of Richard Burton. Kate arranged a blind date between Jane and Bradley Whitford, and the couple began a romantic relationship that would eventually lead to their marriage in 1992.
Two years of dating preceded their wedding, and the couple welcomed their three children: Frances, born in 1997, Edward, born in 1999, and Mary, born in 2002.