James William Denver was born on October 23, 1817 at Winchester, Virginia. In 1830, he moved to Ohio with his parents Patrick (1787-1858) and Jane (Campbell) Denver (1794-1874) and siblings, who settled near Wilmington. Denver studied civil engineering, briefly taught school in Missouri, and then studied the law, graduating from the Cincinnati Law School in 1844.

In 1845, Denver returned to Missouri, where he practiced law at Platte City. In March 1847, he organized Company H of Missouri's Twelfth Infantry Regiment, serving as captain until the close of the Mexican War in July 1848. He then returned to Platte City and in 1850 moved to California, where he was elected to the State Senate in 1851, appointed secretary of state in 1852, and elected to the U.S. Congress in 1854.

At the end of his Congressional term, Denver was named Commissioner of Indian Affairs, on April 17, 1857. He resigned from this office to become Governor of the Territory of Kansas on June 17, 1857, taking over from fellow Democrat Frederick P. Stanton. During his administration, the capital of Colorado (then in Kansas Territory) was founded and named Denver in his honor. Hugh Sleight Walsh briefly served as acting territorial governor while Denver was on leave in July and again after Denver resigned in October 1858.

From November 1858 to March 1859, Denver served again as Commissioner of Indian Affairs, and in August 1861 he was commissioned brigadier general in the Union Army. Denver resigned from the Army in March 1863 and resumed practicing law in both Washington, D.C. and Wilmington, OH. He was a delegate to the Democratic National Conventions in 1876, 1880, and 1884.

Denver married Louise Catherine Rombach (1833-1914) in 1856. They had at least four children: Katharine St. Clair (Denver) Williams (1861-1937), James William (1863-1898), Matthew Rombach (1870-1954), and Mary Louise (Denver) Lindley (1871-1942). James William Denver died on August 9, 1892 at Washington, D.C. and was buried in Wilmington, OH.