Melissa Usher grew up in Higganum, Connecticut, and entered Mount Holyoke Female Seminary in 1852. She remained for that academic year, returned in 1854, and graduated with the Class of 1856. After graduation she took care of her ill mother, married Alpheus Williams Tyler and had three children. Her sister Jerusha (Jessie) Usher also attended Mount Holyoke Female Seminary and graduated in 1857. Melissa Usher Tyler died in Tylerville, Connecticut in 1906.