Mossengo-Omba said he was retiring but his departure comes amid a crisis of confidence in the organisation's leadership, with a growing fallout over the decision to strip Senegal of the Africa Cup of Nations title and calls for an investigation into alleged corruption at African football's governing body.
There has been a swell of recent criticism of his staying on as general secretary well past the organisation's mandatory retirement age of 63, largely on social media but also from members of CAF's executive committee.
"After over 30 years of an international professional career dedicated to promoting an ideal form of football that brings people together, educates, and creates opportunities for hope, I have decided to step down from my position as Secretary General of CAF to devote myself to more personal projects," Mossengo-Omba said in a statement.
"Now that I have been able to dispel the suspicions that some people have gone to great lengths to cast on me, I can retire with peace of mind and without constraint, leaving the CAF more prosperous than ever.
"I sincerely thank the CAF's 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. Let us hope that the progress made will last and be sustained," he concluded.
Mossengo-Omba has been a divisive figure at CAF, accused by some employees of creating a toxic atmosphere at the workplace, although an investigation after staff complaints cleared him of any wrongdoing.
The 66-year-old is of Congolese origin but a Swiss citizen and former FIFA employee who was a university friend of FIFA president Gianni Infantino.
Although the statement said he was retiring, Mossengo-Omba's statement was contradicted by Motsepe at a later press conference.
"He told me he has been asked by the DR Congo president to go and help with football development in that country," said Motsepe.
It is expected that Mossengo-Omba will run for the post of president of the Democratic Republic of Congo's football federation in elections in the coming months, sources told Reuters.
If successful, that would thrust him into contention for CAF's top job should Motsepe resign to enter politics in his native South Africa, where he is being touted as a possible successor to President Cyril Ramaphosa. Motsepe has, however, denied this.
Earlier this month, Motsepe admitted CAF was struggling with questions over its integrity and, in the wake of the Cup of Nations final controversy, Senegal's government has called for an international investigation into the running of the organisation.
Stripping Senegal of the Cup of Nations title was a decision made by CAF's Appeals Board but as a result there has been a heavy toll on the image of the African game.
CAF said later on Sunday that its competitions director Samson Adamu would take over as acting general secretary.