He was educated as a physician at McDowell"s Medical College in Saint Louis, Missouri.
Glenn served with Colonel Alexander William Doniphan"s Missouri Volunteers in the Mexican-American War, returning to Saint Louis afterwards to marry Nancy Harrison Abernathy, a relative of Tirey L. Ford, on March 15, 1849. In 1850, Glenn joined the California Gold Rush. He found no gold, but was successful in operating a livery stable at Sacramento, later selling it for a good profit.
He returned to California in 1853, bringing his family with him.
Glenn became a cattle rancher, and in 1868 moved to Jacinto, California, then in Colusa County. He purchased nearly 45,000 acres, cultivating 6,000 of them in grain, earning him the nickname of the Wheat King of California.
His newphew, Tirey L. Ford worked on his ranch for three years and later became Attorney General of the State of California. Glenn began his public career on the California State Board of Agriculture.
In 1879, he ran in the California gubernatorial election as the candidate of both the Democratic and the New Constitution parties.
He lost to Republican George C. Perkins. In 1883, Doctor Glenn was murdered on his ranch at Jacinto by Huram Miller, who worked for him as a bookkeeper. Miller was an alcoholic and Glenn finally struck him, after being verbally abused by the drunken employee.
Miller brooded for several days, then shot Glenn in the head from ambush with a load of buckshot.
In 1891, Glenn County was created and named in honor of Hugh James Glenn.