George Henry Dern was born in Nebraska in 1872 to German immigrants John Dern and Elizabeth Dern, who had immigrated to the United States when they were children. Both Elizabeth and John came from prominent families. They married in 1870, and by the 1880s John was operating a grain elevator and managing a lumber business. He became a state senator and served as state treasurer. In 1890 he became involved in a business enterprise in an old abandoned silver mine in Lewiston, Utah. John and his business partners utilized a special cyanide solution to leach gold out of the ore at a gold ledge in the mine. After 1892, John became president of the Mercur Gold Mining and Milling Company, and moved his family to Salt Lake City, including the children Mary (b. 1871), Mathilde "Tillie" (b. 1875), Fredie (b. 1877), Elizabeth "Lizzie" (b. 1879), and Arthur (b. 1880).

George did not join his parents and siblings in Salt Lake City just yet. He was the star player and captain of the University of Nebraska's football team, played saxophone in the school band, and loved English and writing. In 1894 he came to Salt Lake City and worked as a bookkeeper for Mercur Gold Mining and Milling Company, and soon became the company treasurer.

George married Charlotte "Lottie" Brown, a fellow Nebraskan whom he met in Salt Lake City, in an elaborate wedding on 7 June 1899. Together the couple would have the following children: Mary Joanna Dern (1902), John Henry Dern (1903), William Brown Dern (1906), Margaret (1909), Elizabeth Ida (1915), and James G. (1916). Tragically, Margaret died of a sudden illness shortly before her first birthday.

In 1901 Dern was promoted to general manager of the now Consolidated Mercur Gold Mines Company. Dern and Theodore P. Holt developed the Holt-Dern roaster, a mechanism by which silver could be recovered from low-grade ores. Mercur was the largest gold mine in Utah until the last of the gold was extracted in 1913.

George Dern's political career began when he was elected to the Utah State Senate in 1914 on the Democratic/Progressive fusion ticket. He served until 1923, and was Democratic floor leader twice. Dern introduced and sponsored to successful passage progressive measures such as the Workmen's Compensation Act, Corrupt Practices Act, Mineral Leasing Act, Blue Sky Law, and Initiative and Referendum.

In 1924 he ran for state governor against incumbent Charles R. Mabey, winning by over 10,000 votes. Dern was re-elected by a landslide in 1928. Governor Dern was known as outgoing, open-minded, and empathetic. He was dedicated to developing Utah's natural resources, education, social welfare, and reforming Utah's tax laws. He organized public land states to pass the Jones Act, which granted to the land grant states all mineral rights in their school lands. Dern called and was chairman of the Colorado River Conference, which gained recognition from committees in Washington that the waters of Western streams belonged to the states and not the federal government. He was also active in getting federal aid for Utah roads.

As governor, Dern served twice as Chairman of the National Conference of Governors, where he met fellow Democrat and New York Governor Franklin Delano Roosevelt. Dern served as Secretary of War in President Roosevelt's first cabinet. As head of the War Department during peace time, Dern was not primarily involved in New Deal programs except for overseeing the administration of the Civilian Conservation Corps.

George Henry Dern died in office in 1936 from heart and kidney complications following influenza. He belonged to the Congregational Church, was a Past Grand Master of Masons, 33rd degree Scottish Rite Mason, Knight Templar, Past Potentate of the Nobles of the Mystic Shrine, member of the American Institute of Mining and Metallurgical Engineers, Delta Tau Delta Fraternity, belonged to the Chamber of Commerce, and was a member of the University, Alta, and Salt Lake Country Clubs. The Dern family home, located at 715 E. South Temple in Salt Lake City, was demolished in 1970.