He was the son of President Thomas Jefferson's daughter, Maria Jefferson Eppes, and John Wayles Eppes, former Senator from Virginia and member of Virginia House of Representatives. He was born at "Eppington" Chesterfield County, Virginia. On November 28, 1822. At "Ashton," Albemarle County he married his first wife, Mary Elizabeth Cleland Randolph. She passed away April 15, 1835 near Tallahassee, Leon County, Florida.
Francis moved his family to Tallahassee, Florida after his grandfather died. He was a planter and served several terms as intendant (mayor) of Tallahassee, Florida. He was very active in the Episcopal Church holding meetings at his home before a church was built. He was instrumental in creating FSU in Tallahassee, and there is a bronze statue of him on the grounds. There is also a scholarship named for him. In 1996, the Jefferson-Eppes trophy was established to be awarded to the winner of the Florida State/University of Virginia football game. The trophy consists of a silver pitcher presented to Eppes in 1842 by the citizens of Tallahassee. It sits on a block of the "McGuffey Ash" that was planted on the grounds of the University of Virginia in 1826 - about the time of the opening of the University. The University of Virginia was the first winner of the trophy.
He was appointed justice of the peace in Leon County, Florida on February 17, 1833. On March 15, 1837 Francis remarried, a widow, Mrs. Susan Margaret Ware Crouch, daughter of Governor Nathaniel Ware of Georgia. He served a number of terms as Mayor of Tallahassee, and was involved in the founding of the Diocese of Florida, and served as the Diocesan Secretary for many years. He had 13 children with two wives, and is buried with his second wife in Greenwood Cemetery in Orlando, Florida. There is an Eppes-Shine plot in that cemetery.
In 1864 Eppes sold his plantation and invested the proceeds in the Confederate cause. After the Civil War he was in financial ruin. In 1869, he sold his Tallahassee home and all his belongings to pay off his debts, and started a new life as a citrus grower. He moved his family to Orange County, Florida near Orlando. He was still active in the Episcopal church. He died in 1881 at "Pine Hill" among his orange groves on the west side of Lake Pineloch south of Orlando at the age of 80. It was a long way from the Eppington, Monticello, and Poplar Forrest plantations of his boyhood.
He was known as Francis Wayles Eppes VII not Senior. All the Francis Eppes before him have a number, and they go way back to I.