Franklin, 63, was executed at the state prison in Bonne Terre for killing Gerald Gordon in a sniper shooting at a suburban St. Louis synagogue in 1977. Franklin was convicted of seven other murders across the country and claimed responsibility for up to 20 overall, but the Missouri case was the only one that brought a death sentence.
Mike O'Connell, of the Missouri Department of Corrections, said Franklin was pronounced dead at 6:17 a.m.
The execution was the first in Missouri using a single drug, pentobarbital.
Franklin's fate was sealed early Wednesday when the U.S. Supreme Court upheld a federal appeals court ruling that overturned two stays granted Tuesday evening by district court judges in Missouri.
Franklin also admitted to shooting and wounding civil rights leader Vernon Jordan and Hustler magazine publisher Larry Flynt, who has been paralyzed from the waist down since the attack in 1978.
Franklin, a paranoid schizophrenic who grew up in Mobile, Ala., was in his mid-20s in 1977 when he began drifting across America, robbing up to 16 banks to fund his travels.
He bombed a synagogue in Chattanooga, Tenn., in July that year. No one was hurt, but the killings began soon after that, many of them sniper shootings.
Franklin had a particular dislike for interracial couples - several of his victims were black men and the white women with them.
He arrived in suburban St. Louis and picked out Brith Sholom Kneseth Israel synagogue from the Yellow Pages. On Oct. 8, 1977, a bar mitzvah ended and guests were in the parking lot when Franklin opened fire from a grassy area nearby, killing Gordon, 42.
The killings continued for three more years. Franklin was finally caught after killing two young black men who were about to go jogging with two teenage white girls in Salt Lake City in August 1980.
Years later, in federal prison, he admitted to the St. Louis County killing. He was sentenced to death in 1997.
Franklin, in the days leading up to the execution, said in several interviews that he was sorry for his crimes and was no longer a racist.