He attended local schools until age 16, when he went to work as a clerk in the shipping house of Peter Wright and Sons. He became a partner in the business in 1862. In 1872 he became vice-president of the International Navigation Co., which operated a fleet of twenty-six steam ocean liners known as the Red Star Line. By 1888, he was president of both companies and of the American Line. In 1902, with financing from J. Pierpont Morgan, the companies were merged into the International Mercantile Marine shipping trust company, which operated 136 vessels over five transatlantic lines. Griscom later served as the IMM's first President.
Dolobran (1881), his country house in Haverford, Pennsylvania, is one of architect Frank Furness's most significant houses. Furness also designed interiors for two of Griscom's Red Star Line steamships, the S.S. St. Louis (1894–95) and the S.S. St. Paul (1894–95). Griscom established and owned a private hunting plantation north of Tallahassee, Florida called Horseshoe Plantation.
Griscom died of a stroke at the age of 71.
Griscom married Frances Canby Biddle (1840-1923) in 1862, and they had six children:
- John Acton Griscom (1863-1865).
- Helen Biddle Griscom (1866-1950), married (1889) Samuel Bettle.
- Clement Acton Griscom Jr. (1868-1918), shipping executive, married (1889) Genevieve Sprigg Ludlow. Their children were Ludlow, Joyce, and Acton.
- Rodman Ellison Griscom (1870-1944), stockbroker, married (1897) Anne Starr.
- Lloyd Carpenter Griscom (1872-1959), diplomat, married (1901) Elizabeth Duer Bronson.
- Frances C. "Pansy" Griscom (1879-1974), champion golfer.
Mother and Daughter (Mrs. Clement Griscom and Frances C. Griscom) (1898) by Cecilia Beaux.
Helen Biddle Griscom (1893) by Cecilia Beaux.
"Horseshoe Plantation," Leon County, Florida.
- Elizabeth Werbe, Victorian Life in Haverford, Pennsylvania (Bryn Mawr College, 1997).
- "Merger of the Steamship Lines" New York Times, April 21, 1902.
- George E. Thomas, et al. Frank Furness: The Complete Works (New York: Princeton Architectural Press, 1996 revised edition), p. 316.
- Ninigret statue from SIRIS.
- Ninigret photo from Flickr.
- Clement A. Griscom Jr.
- Davis, William E., Jr. (1994). Dean of the Birdwatchers: A Biography of Ludlow Griscom. Washington, D.C.: Smithsonian Institution Press. ISBN 1-56098-310-8.