Botha played his first boxing match as a professional in 1991. On 9 December 1995 he got the chance to fight for the vacant IBF heavyweight title against Axel Schulz. The confrontation took place in Stuttgart at the Hanns -Martin -Schleyer -Halle. Botha, who was victorious in 35 previous fights, Schulz defeated just by points. The fight was not considered, however, a little later because of a positive doping tests Botha and again declared the title vacant.
Exactly eleven months later Botha got another opportunity to fight the IBF title. However, he lost in Las Vegas against Michael Moorer technical knockout in the twelfth and final round. In the following years, Botha denied, among other fights against Mike Tyson and Shannon Briggs. Against Tyson he lost by whacked in the fifth round, against Briggs he boxed a draw. However, he was allowed to play against the world champion Lennox Lewis on July 15, 2000, but was defeated by technical knockout in the second round.
On March 16, 2002 Botha boxed for the time being the last time a championship belt. In Stuttgart he rose against WBO title holder Wladimir Klitschko in the ring. But his fourth shot at the title he had wasted and lost by technical knockout in round eight. His preliminary final boxing match ended four months later in a draw against Clifford Etienne.
From 2003 to 2006 Francois Botha appeared regularly at the K -1. In his twelve fights he could win against Jérôme Le Banner and Peter Aerts. Le Banner could not compete because of a recently recovering from injury to the fourth round, and Peter Aerts had to retire due to a leg injury. After several successive defeats, he finished his K-1 career, focusing since 2007 on boxing.
In his comeback fight he defeated on July 6, 2007, Australian Bob Mirovic on points, then stopped again, however, more than 1.5 years inactive, and then on February 6, 2009 US- American Ron Guerrero in the fight for the vacant world title the beating of little significance World Boxing Foundation ( WBF ). In his first title defense, he won on May 15, 2009 in Magdeburg against the German Timo Hoffmann 2-1 after judges votes. Botha was taken thereupon by the German SES boxing stable for three fights under contract. Then a struggle for October 24, 2009 in Dessau was planned against Willi Fischer, but the fishermen injured canceled at short notice. Botha boxed instead against Pedro Carrión and defended his title against Cuban after a controversial judgment ( 114:114, 115:115, 114:113 ) by a draw. The WBF confirmed the point standings.
His next title defense should (Uganda) held first on January 16, 2010 in Kampala against the former heavyweight champion Evander Holyfield. The battle, however, was postponed several times due to financial and organizational difficulties, and finally laid on April 10, 2010 in Las Vegas. Botha was defeated in the battle against the 47-year veteran Holyfield technical knockout in the eighth round.