The Egyptians will miss the finals for the second time in a row, representing a major setback for American coach Bob Bradley who was hired last year after they had failed to qualify for the 2012 edition.
Foxi Kethevoama put Central African Republic in front midway through the first half and the visitors equalised with a goal from Emad Moteab 13 minutes from time.
Egypt's 3-2 home defeat in Alexandria in the first leg was one of the biggest ever upsets in Nations Cup qualification.
Central African Republic are now through to the last round of qualifying for the 2013 finals in South Africa.
Thirty teams will be drawn on Thursday into 15 final round, two-legged knockout ties to be played in September and October.
The winners go to the finals in January, along with the host nation.
Egypt have won a record seven Nations Cup titles, three of them in a row in an unprecedented spell of dominance from 2006 to 2010.