Moussa Sow scored on minutes 33 and 53 to secure a ticket to the finals for the Teranga Lions.
Senegal remain on top in Group E with 13 points. They also have the best record of any team so far in the qualifiers.
Cameroun are now second in Group E with 8 points after they beat Mauritius 5-0 on Saturday.
The loss leaves the Leopards in third place with 7 points. With only one game left to play, they can no longer qualify as one of the two best runner-ups who will join the winners of each group.
Changing coaches a few days before the game, and even the return of Tresor Mputu Mabi to international competition, did not help the Leopards against a Senegalese team determined to clinch its qualification at home.
The Leopards will play their last game against Cameroun on October 9 in Kinshasa.
The Leopards failed to qualify for the 2010 Africa Cup of Nations finals held in neighboring Angola. They will now also be absent next year in the finals hosted in two Central African countries, Equatorial Guinea and Gabon.