Harris Hawthorne Wilder was born in Bangor, Maine, on April 7, 1864. He was the only child of Solon Wilder and Sarah Watkins Smith. His father was a noted musical director and composer in New England, who published a book of church hymns in 1874, including a number of original pieces. His most recognized composition was an arrangement of Augustus Toplady's Rock of Ages, using a responsive double chorus. Harris Hawthorne Wilder takes his lifelong nickname, "Hallie," from his father's musical proclivities, a name drawn from Handel's Hallelujah Chorus, referring to Solon Wilder's fondness for grand oratorios.

His mother, Sarah "Sally" Wilder, was the family homemaker, who continued in this role for her adult son until her death in 1907. She came from a family of physicians, including her father, Chandler Smith, and three uncles. Although Wilder's maternal grandparents died too early to influence him directly, Wilder later cited his mother's family for his original interest in biological and anatomical matters.

Harris Wilder lived the first three years of his life in Bangor, as his father served as chorister at the French Street Congregational Church. In 1888, the family moved to the Boston area where Solon Wilder accepted a teaching position at the Boston Conservatory of Music. He was also chorister at the Shepherd Memorial Church in Cambridge. During the Wilders' stay in Cambridge, Sarah Wilder's recently widowed sister, Eliza Gardner Smith, lived with the Wilder family. Wilder credits his "Aunt Lizzie" with inspiring him toward a life of learned curiosity, as well as instructing him in drawing, a talent that marked his professional career and one evident throughout this collection of his personal papers. "Aunt Lizzie's" daughter, and Harris Wilder's cousin, Rebecca Wilder Holmes, eventually joined Harris Wilder at Smith College as a professor of music.

In 1871, prompted by Solon Wilder's poor health, the Wilder family moved to Princeton, Massachusetts, and lived with Solon Wilder's parents, Ivory and Louisa Wilder. During the following years, Solon Wilder expanded his reputation by organizing and conducting a number of musical festivals throughout New England, plus a number in the Midwest. In 1871, a young Harris Wilder accompanied his family on one tour to Pennsylvania, Minnesota, and finally to Missouri, where he investigated the caves made famous by Mark Twain in Tom Sawyer. Solon Wilder died of tuberculosis in 1874, when Harris Wilder was ten years old.

Inspired by his mother and his "Aunt Lizzie," Harris Wilder showed a bent toward scientific investigation from a young age. As a boy, he would cut out paper dolls like many children, but would then diagram their skeletons. When Wilder was six, a family friend presented him with a seven-month human embryo skeleton. He was also given a human skull by another aunt. He often brought home carcasses of woodchucks and skunks in order to reconstruct their skeletons. While living in Cambridge, he built his own museum containing numerous skeletons. When he was a young adolescent, a local physician, Joseph O. West, helped him unearth the doctor's dead horse, "Thomas Equinas," so Wilder could study the horse's anatomy. By the age of fourteen, he was regularly corresponding with Alfred Wially, a French scientist living in London, and exchanging silk-producing moth cocoons.

Growing up in Princeton, a summer retreat community near Mt. Wachusett, afforded Wilder the opportunity to meet many interesting and successful people boarding in his family's home. Some of the children of these visitors became lifelong friends. In 1880, he traveled to Worcester to attend high school, returning home on the weekends. As a young student, he took part in numerous musical productions, a talent he utilized throughout his later life at Smith College.

Wilder family's financial resources were limited and only with a gift from the Chickering family, regular summer boarders at the Wilder house, could he attend college. Daughter May Chickering remained a friend throughout Wilder's life. In 1882, Wilder enrolled at Amherst College, studying zoology and classics. There he met Professor John Tyler, who had just introduced a biology department at Amherst. Tyler would become a main influence in Wilder's professional life.

After receiving his A.B. from Amherst in 1886, Wilder taught biology for three years in the Chicago public school system. In 1889, motivated by Tyler who had also studied in Germany, Wilder traveled to Freiburg University, a noted center of amphibian research, to pursue a doctorate degree. He Studied with Robert Wiedersheirn and August Weismann and received his Ph.D. in 1891. A minor subject of his examination was medieval English. He returned to the United States and taught again in Chicago. Wilder's mother accompanied her son in all his career moves. A year later in 1892, Wilder obtained a position at Smith College. He would remain at Smith for the next thirty-six years.

Wilder's professional achievements and his contributions to the Smith College curriculum were numerous. In his second year at Smith, Wilder founded the school's Zoology Department. Two years later he added fieldwork to the curriculum, a rare notion at that time. By the early 1900s, his classes, especially those in evolution and anthropology, were overenrolled by both majors and non-majors. He was an active researcher and writer, publishing either an article or a book nearly every year of his professional life. He produced five major books: , , , , and . His primary areas of research were amphibian studies, primate and human identification using palm and sole prints, teratology (the study of genetic malformations) among human twins, comparative anatomy, and physical anthropology, including the excavations of skeletal remains of indigenous Indian races of Massachusetts. Notable achievements included the discovery of a species of salamanders without lungs or gills, and the development of a system for reconstructing a lifelike human face solely from the measurements taken from a deceased individual's skull. Although interested in the study of eugenics, a popular field at the turn of the century, Wilder differed with many of his colleagues by suggesting that the differences between races, which to Wilder were often evolutionary adaptations to climate, should be celebrated by science, not used as a means of social and political separation.

In 1901, Wilder met Inez Whipple, one of the Zoology Department's first graduate students. The two co-taught a class in 1906, "Anatomy and Physiology of Man." That same year, Wilder and Whipple were married. In 1914, Inez Whipple Wilder became a full professor at Smith. The couple frequently worked together in their research. The Wilders led an active social life in the Northampton community, and their Belmont Street house, which was located a block from campus and built from a plan of an Italian villa, became a popular gathering place for friends, students, and visiting scholars. Their life together included many travels to Egypt, Jamaica, and southern Europe. In 1920, Harris Wilder taught at Ginling University in Shanghai, China. Following the Wilders' return from China, their home became a center for visiting students from China.

Wilder died of a cerebral hemorrhage on February 27, 1928. He was working on his autobiography when he died. Inez Wilder completed the early stages of this project before her own death a year later.