Mudd was born in Maryland, attended Catholic schools, and became a medical doctor. He first met John Wilkes Booth at St. Mary's Church in Bryantown, Maryland in 1864. Mudd treated the wounded Booth during his escape following the assassination of President Abraham Lincoln on April 14, 1865. Mudd was tried as part of the conspiracy to kill the president (he was represented by the son of Thomas Ewing), convicted, and spent four years in prison before he was pardoned by President Andrew Johnson. The question of Mudd's guilt or innocence is one of the great popular disputes of American history and his grandson Richard Mudd (d. 2002) dedicated tremendous effort to clearing his grandfather's name.