In 1845 he moved to Columbus, Ohio, and enrolled in Starling Medical College. His uncle, Dr. Rufus Gilpatrick was one of the instructors. Graduating in February, 1849, he moved to New Madison, Ohio and on January 15, 1850 married Nancy G. Putman. He practiced medicine and took an active role in county politics as a member of the Republican Party.
In 1856 Blunt relocated to Anderson County, Kansas, following his uncle who had moved there several years earlier. He soon became involved in the conflict known as Bleeding Kansas. During a confrontation with the pro-slavery territorial government in 1857, Blunt joinded a force including Jim Lane and abolitionist John Brown.
Blunt was a key member of the Wyandotte constitutional convention that framed the Kansas state constitution in 1859, and served as chair of the committee on militia.
Blunt was appointed to command the District of the Frontier. He campaigned for control of the Indian Territory and won a victory at the Battle of Honey Springs, bringing much of the Indian Territory into Union control. In October of 1863, while moving his headquarters from Fort Scott to Fort Smith a Confederate force under William C. Quantrill approached. Quantrill's Raiders routed and killed over 80 of Blunt's 100 escorts, including his adjutant Major Henry Curtis, son of Major General Samuel Curtis. These actions led to his removal from command of the District of the Frontier. In 1864, Blunt was able to redeem himself. Confederate Maj. Gen. Sterling Price began an invasion of Missouri and Blunt took command of the 1st Division of Army of the Border. He and the cavalry under Alfred Pleasonton fought delaying actions until Samuel R. Curtis brought the full strength of the army together and inflicted a defeat on Price at the Battle of Westport. Blunt's division inflicted the final defeat to Price at the Second Battle of Newtonia. Blunt commanded the District of South Kansas when the war ended.
Blunt's behaviour became erratic in 1879 and he was committed to an asylum. He died two years later with the cause of death given as "softening of the brain." His body was returned to Leavenworth and is buried in the Mount Muncie Cemetery.