Born in Farmington, Missouri, he was raised in a highly religious family which included several generations of devout Methodist preachers. During his early teens, Asbury, along with his siblings Mary, Emmett and Fred Asbury, became disenchanted with the local Southern Methodist church.

During World War I, Asbury enlisted as a private in the United States Army. He was later promoted to sergeant, and then to second lieutenant. He served in France until he was seriously wounded during a gas attack (his lungs were severely damaged and would result in health problems throughout his life). He eventually received an honorable discharge on January 1919.

Asbury achieved first notoriety with a story that H. L. Mencken published in his magazine, The American Mercury in 1926. The story detailed a prostitute from Asbury's hometown of Farmington, Missouri. The prostitute took her Protestant customers to the Catholic cemetery to conduct business, and took her Catholic customers to the Protestant cemetery; some in Farmington considered the prostitute beyond redemption.

The article caused a sensation: The Boston Watch and Ward Society had the magazine banned. Mencken then journeyed to Boston, sold a copy of his magazine on Boston Common, and was arrested. Sales of the recently-founded Mercury boomed, and Asbury was a celebrity. Asbury then focused his attention of a series of articles debunking temperance crusader Carrie Nation.

Herbert continued working as a reporter for various newspapers including the Atlanta Georgian, the New York Sun, the New York Herald and the New York Tribune. In 1928, he decided to devote his time exclusively to writing. During this time, he wrote numerous books and magazine articles on true crime. He was also involved in screenwriting and wrote several plays which appeared on Broadway. None were successful.

He married Edith Snyder in 1945, a journalist ultimately employed by The New York Times where she spent most of her career as a reporter.

After his final book The Great Illusion: An Informal History of Prohibition in 1950, he retired from writing. Asbury died on February 24, 1963 at the age 73 from a chronic lung disease.

The 2002 film Gangs of New York revitalized interest in Asbury and many of Asbury's works, mostly chronicling the largely hidden history of the seamier side of American popular culture, have been reissued. In 2008, The Library of America selected an excerpt from Gangs of New York for inclusion in its two-century retrospective of American True Crime.

Although his books have long been popular within the true crime genre, commentators such as Luc Sante, Tyler Anbinder and Tracy Melton have suggested that Asbury took journalistic liberties with his material. On the other hand, Asbury's books have lengthy bibliographies, noting the newspapers, books, pamphlets, police reports and personal interviews he drew upon for his works. But his books, having been written for popular audiences, do not have in-text citations, which would make it easier to check the accuracy of his sources.

In 2005, Tracy Melton claimed in his book Hanging Henry Gambrill: The Violent Career of Baltimore's Plug Uglies, 1854-1860 that the Plug Uglies were actually a Baltimore-based gang. New York newspapers compared the Dead Rabbits to the Baltimore Plug Uglies following the July 4, 1857 riots, which occurred just a month after Plug Ugly involvement in the Know-Nothing Riot in Washington. Melton further speculated that Asbury had apparently read these accounts and inaccurately incorporated the Plug Uglies into his book The Gangs of New York.

Asbury is credited with several crime-thriller screenplays for Columbia Pictures, which he co-wrote with Fred Niblo Jr (1903-1973):

• Gangs of New York (1938)
• Name the Woman (1934)
• Among the Missing (1934)
• Fugitive Lady (1934)