Browne was born in Waterford, Maine. He began life as a compositor and occasional contributor to the daily and weekly journals. In 1858, he published in the Cleveland Plain Dealer the first of the "Artemus Ward" series, which, in a collected form, achieved great popularity in both America and England. In 1860, he became editor of Vanity Fair, a humorous New York weekly, which proved a failure. About the same time, he began to appear as a lecturer and, by his droll and eccentric humor, attracted large audiences.
"Artemus Ward" was the favorite author of U.S. President Abraham Lincoln. Before presenting "The Emancipation Proclamation" to his Cabinet, Lincoln read to them the latest episode, "Outrage in Utiky", also known as High-Handed Outrage at Utica.
Ward is also said to have inspired Mark Twain when Ward performed in Virginia City, Nevada. Legend has it that, following Ward's stage performance, he, Mark Twain, and Dan De Quille were taking a drunken rooftop tour of Virginia City until a town constable threatened to blast all three of them with a shotgun loaded with rock salt.
In 1866, Ward visited England, where he became exceedingly popular both as a lecturer and as a contributor to Punch. In the spring of the following year, Ward's health gave way and he died of tuberculosis at Southampton on March 6, 1867.
After initially being buried at Kensal Green Cemetery, Ward's remains were removed to the United States on May 20, 1868.