Chandler, who was born in Boston, Massachusetts, graduated from Harvard in 1861 and then acted as assistant to Benjamin Gould, an astronomer with the US Coast Survey, from 1861 to 1864. He remained with the Survey until 1870 when he started work as an actuary, returning to scientific work with the Harvard Observatory in 1881. From 1885 he devoted himself to private research.

Chandler is best known for his discovery of the variation in the location of the geographic poles – and, hence, of the variation in latitude of points on the Earth's surface. In 1891 he announced the discovery of a 428-day cycle during which latitude varied by 0.3 second. This variation in the Earth's rotation became known as the Chandler wobble and was soon confirmed by the International Latitude Service, established in 1900.