Born in Western New York, Locke finished his education at the age of 12 and moved to Richland County, Ohio as a printer's assistant. He began his journalism career in Plymouth, Ohio in 1852 when he started The Advertiser. In 1855 he moved on to Mansfield to write for the Herald, followed a year later by a move to Bucyrus and then in November of 1861, he moved to Findlay to take over the Hancock Jeffersonian. While in Findlay, Locke introduced the Nasby Letters. Using satire to support Lincoln and The Civil War under the pseudonym of Petroleum Vesuvius Nasby, an ignorant, violent, prejudiced pro-slavery supporter, the Nasby Letters quickly became popular during the Civil War and appeared in newspapers across the northern United States.

In 1865,  he arrived in Toledo and made the Toledo Blade a weekly national, as well as a local daily paper, and continued his Nasby Letters, calling for social justice and reform. 

President Abraham Lincoln, opened some of his meetings by reading selections from the latest Nasby letters. Some say the night he died, the President delayed his trip to Ford's Theater by entertaining his guests with a reading from the Nasby Papers. After the Civil War, a member of President Grant’s cabinet said, “The North won the Civil War by three forces: the Army, the Navy, and the Nasby papers.”

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Locke's popularity grew after the Civil War through books, lectures and newspapers. His satirical use of backwards characters became a popular style in American literature.