George Henry Dern was born September 8, 1872, in Scribner, Nebraska, to Elizabeth and Johannes (John) Dern, German immigrants. He grew up on a family farm and attended Nebraska Normal and Business College, graduating in 1888. His family moved to Utah in 1895, where both Dern and his father worked in the mining industry. Dern eventually became general manager of the Consolidated Mercur Gold Mines Company and was a co-inventor of the Holt-Dern roaster, a roasting process for the reduction of refractory ores. Dern was an officer and director of a number of mining and metallurgical enterprises and commercial companies, including the Holt-Christensen Process Company, Pleasant Grove Canning Company, First National Bank of Salt Lake City, Mutual Creamery Company, and the First Security Trust Company.

Dern married Charlotte "Lottie" Brown on June 7, 1899, in Nebraska. They had five children: Mary, Elizabeth, James, John, and William. He was a member of the Congregational Church and a 33rd degree Mason, a Knight of Templar, and a Shriner.

In 1914, Dern was elected to the Utah State Senate representing Salt Lake County, serving for eight years. He introduced the Workmen’s Compensation Act, Corrupt Practices Act, Mineral Leasing Act, Blue Sky Law, and Initiative and Referendum.

In 1924, Dern was elected governor of Utah, running as a Democrat against Republican incumbent Charles Mabey. Dern was re-elected in 1928. While governor, he served twice as chair of the National Governors' Conference and adopted a state income tax and a corporate franchise tax. Dern organized the public land states to help pass the Jones Act and chaired the Colorado River Conference, which fought for states rights to control river water. Dern finished his second term as governor in January 1933.

On March 4, 1933, Dern was appointed Secretary of War under Franklin D. Roosevelt. As secretary, Dern was involved in upgrading the intracoastal waterway system, especially the Mississippi and St. Lawrence Seaway. He also toured United States military installations in the United States, including Hawaii, the Philippines, and Puerto Rico. He also visited China and Japan.

George Henry Dern died at age 64 on August 27, 1936, from heart and other complications resulting from past influenza attacks. He was buried in Mount Olivet Cemetery in Washington, D.C.