Stunned 3-2 at home in a delayed first leg played behind closed doors two weeks ago, the Pharaohs fell behind midway through the first half in Bangui when captain Foxi Kethevoama scored.
Veteran striker Emad Moteab, one of four players brought into the side by American coach Bob Bradley after the Alexandria debacle, levelled late in the second half, but the visitors never looked like scoring the other two goals they needed to salvage the tie.
After winning a record three titles on the trot between 2006 and 2010, Egypt finished last behind Niger, South Africa and Sierra Leone in a 2012 qualifying group.
Now they have fallen at the first hurdle on the road to the 2013 finals in South Africa after starting as strong favourites to eliminate opponents ranked 14 places lower in Africa.
Central African Republic, who have never come close to qualifying for African football's showpiece tournament, will join 29 other countries for a final-round qualifying draw on 5 July in Johannesburg.