The Pierce Family Correspondence consists primarily of letters to and from the children of John Pierce and his first wife, Mary (Paterson) Pierce, as well as of his second wife, Mary (Goodman) Pierce. The collection documents events of national importance: John Pierce, a colonel and paymaster in the Continental Army, received letters from numerous correspondents concerning military, administrative, and political news of the American Revolution. Moreover, the Pierce brothers traveled extensively along the East Coast as well as in the South, and their letters provide a record of the industrial and social development, natural resources, and scenery of the major cities of the early American republic as well as contemporary opinions on the condition of slavery in America.

Since Timothy Pierce was a doctor, many of his letters illuminate medical practice during this time, including the difficulties of setting up a private practice and the realities of military medicine. Meanwhile, the letters to Sarah Pierce make references to her role as founder and teacher of the Litchfield Female Academy, a nationally prominent girls' school. The collection includes a letter to Pierce from Harriet Beecher Stowe praising her history textbook and requesting copies of it, correspondence about boarders for the school, and three silk diplomas.

Finally, the letters also shed light on social life in the early republic, as the Pierce brothers frequently attended parties, went on steamboat trips, advised their sisters on deportment, and discussed women's fashions with them.