In 1967 and 1968, it won the African Cup of Champions. The team would be finalist four times successively in (1967, 1968, 1969 and 1970). Mazembe was the first team to successfully defend the African Champions Cup. This feat was finally repeated in 2003 and 2004 by Enyimba.
After 18 years of absence, it returned to the African scene thanks to 38-year-old governor Moïse Katumbi Chapwe.
In November 2009 the team won the CAF Champions League against Heartland 2–2 on aggregate, winning on the away goals rule.
In 2010 they retained the 2010 CAF Champions League, and in December they became the first African side to contest the final of the FIFA Club World Cup after defeating both Pachuca of Mexico 1–0 in the quarter-finals and Internacional of Brazil 2–0 in the semi-finals. In the final on 18 December, they were defeated 3–0 by Internazionale.
By winning the CAF Champions League, they qualified for the 2009 FIFA Club World Cup. In their first match in the quarter-finals they lost 2–1 to Pohang Steelers of South Korea. despite taking the lead in the first half. Following a 3–2 defeat to Auckland City in the fifth placed match they finished the tournament in 6th place.
In 2015, TP Mazembe secured their fifth title in the competition after defeating USM Alger of Algeria 4–1 aggregate in the 2015 CAF Champions League Final.