He was born into a Quaker family in Philadelphia, Pennsylvania, son of Edward M. Davis and Maria Mott Davis (a daughter of the women's advocate Lucretia Mott). He graduated from Harvard University in 1869 and received a Master of Engineering in the following year.

Davis initially worked in Córdoba, Argentina as a Meteorologist for three years and after working as an assistant to Nathaniel Shaler, he became an instructor in geology at Harvard, in 1879. The same year he married Ellen B. Warner from Springfield, Massachusetts. While Davis never completed his PhD, he was appointed to his first full professorship in 1890 and remained in academia and teaching throughout his life.

Davis' most influential scientific contribution was the "geographical cycle", first defined in his 1889 article, The Rivers and Valleys of Pennsylvania, which was a model of how rivers erode uplifted land to base level. His cycle of erosion suggests that (larger) rivers have three main stages of development, generally divided into youthful, mature and old-age stages. Each stage has distinct landforms and other properties associated with them, which can occur along the length of a river's upper, middle, and lower course.

He was a founder of the Association of American Geographers in 1904, and heavily involved with the National Geographic Society in its early years, writing a number of articles for the magazine. Davis retired from Harvard in 1911. He served as President of the Geological Society of America in 1911. He was awarded the Patron's Gold Medal of the Royal Geographical Society in 1919.

Though the cycle of erosion was a crucial early contribution to the development of geomorphology, many of Davis' theories regarding landscape evolution, sometimes termed 'Davisian geomorphology', were heavily criticized by later geomorphologists. When Davis retired from Harvard in 1911, the study of landscape evolution was nearly monopolized by his theories. It was characteristic of Davis to react violently and disdainfully to criticism, particularly to the German criticism in the 1920s headed by Walther Penck; it was also his characteristic to choose to attack the most vulnerable points of that criticism. Since that time, with a less dogmatic approach and greater knowledge, some authors note that Penck's and Davis' ideas have become more compatible and even complementary since the advent of modern tectonic theory. They claim that Davis' ideas are more applicable near active margins where tectonics are "cataclysmic", and Penck's ideas fit better in Models of passive margins and continental platforms.

After his first wife died, Davis married Mary M. Wyman from Cambridge, Massachusetts in 1914, and, after her death, he married Lucy L. Tennant from Milton, Massachusetts in 1928, who survived him.

He died in Pasadena, California, shortly before his 84th birthday. His Cambridge home is a National Historic Landmark.