The immediate events in Sybil at Sixteen occur over a period of less than one week, with references to the previous history of the Sebastian family.

Boston and its nearby areas constitute the major geographical setting although there are relationships with other locations. Most of the action takes place in the stately, lovely but sparsely furnished brownstone house inhabited by Sybil and her parents.

Other places serving as a backdrop for the story include the eldest sister's apartment, a hospital, a library, and other places generally found in large cities. The time of the year is early spring and there are vivid descriptions of the transition from winter to spring in and around Boston.