CAF confirmed that Samson Adamu will take over on an interim basis while the process of appointing a permanent replacement gets underway.
Addressing the media, Motsepe praised Mosengo-Omba for his contribution to the growth and development of football across the continent, describing his tenure as impactful.
"We are enormously grateful to Veron for his contribution to African football and the work he has done for the development and growth of the game on the continent," said Motsepe.
He added that CAF plans to formally honour Mosengo-Omba at a later stage, with an occasion dedicated to recognising his service and contribution.
In his farewell message, Mosengo-Omba said his decision to step down comes after more than 30 years in international football administration, as he looks to focus on personal projects.
"After more than 30 years of an international professional career dedicated to promoting an ideal of football that brings people together, educates and creates opportunities for hope, I have decided to step down," he said.
He also thanked Motsepe, CAF staff, and stakeholders for their role in driving progress within African football.
"I sincerely thank CAF President Dr Patrice Motsepe, my teams, and all those who, directly or indirectly, have enabled CAF and organised African football to make real and remarkable progress," he added.
