Charles Goodnight was born 5 March 1836, in Macoupin County, Illinois. He moved with his family to near Nashville-on-the-Brazos, Milam County, Texas, in 1845. In 1857, Goodnight and his step-brother, John Wesley Sheek trailed a herd of cattle up the Brazos River to the Keechi valley, in Palo Pinto County, Texas. During this time, Goodnight became acquainted with Oliver Loving, who was also running cattle. Goodnight joined Capt. Jack Cureton's rangers, with whom he served as a scout and guide, participating in the raid on 18 December 1860 in which Cynthia Ann Parker was recaptured from the Comanche Indians. In the spring of 1866, Goodnight and Loving organized a cattle drive from Fort Belknap, Texas to the Pecos River, and up to Fort Sumner, New Mexico. This route became known as the "Goodnight-Loving Trail."

In 1869 Goodnight established his Rock Canon Ranch on the Arkansas River, west of Pueblo, Colorado, and married Molly Dyer on 26 July 1870. Goodnight eventually settled in Armstrong County, Texas, where he built a ranch house he dubbed the Home Ranch. After borrowing $30,000 from John G. Adair, Goodnight and Adair launched the JA Ranch, with Goodnight as resident manager. By Adair's death in 1885, the JA Ranch owned 1,325,000 acres, on which grazed more than 100,000 head of carefully bred cattle. As an early believer in improvement through breeding, Goodnight developed one of the nation's finest herds through the introduction of Hereford bulls. With his wife's encouragement, he also started a domestic buffalo herd, sired by a bull he named "Old Sikes," from which he developed the "cattalo" by crossing bison with Angus cattle.

In 1887, Goodnight sold his interest in the JA Ranch, and bought 160 sections in Armstrong County, Texas. He built a ranch house near Goodnight, Texas, into which he and his wife moved on 27 December 1887. He relocated his buffalo herd of 250 head to this ranch, which was organized as the Goodnight-Thayer Cattle Co. After selling his interest in the Goodnight-Thayer Co. in 1900, Goodnight limited his ranching activities to sixty sections surrounding his house. There he continued his experiments with buffalo, and also kept elk, antelope, and various other animals. Goodnight's wildlife preservation efforts gained the attention of such naturalists as Edmund Seymour, and American Bison Society member Martin S. Garretson. Goodnight also grew Armstrong County's first wheat crop, and conducted various agricultural experiments.

The Goodnights had no children. After his wife's death in April 1926, Goodnight became ill, and was nursed back to health by Corinne Goodnight, a young nurse from Butte, Montana. On March 5, 1927, Goodnight married the twenty-six year old Corinne. Shortly afterward they sold the ranch and bought a summer house in Clarendon. Goodnight died on December 12, 1929, in Phoenix, Arizona.