Joseph Franklin was executed early Tuesday morning at the state prison in Bonne Terre.
Franklin was sentenced to death for killing a man outside a St. Louis Synagogue in 1977.
He's been blamed for 22 racially motivated murders in a cross country killing spree from 1977 to 1980.
The execution was scheduled for Wednesday at 12:01 a.m. but was delayed because of court appeals over concerns about the state's plan to use pentobarbital as the lethal drug.
Franklin's lawyers had argued the drug violates the constitution's ban on cruel and unusual punishment.