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Egypt, Equatorial Guinea and Sao Tome e Principe make their first appearances this weekend, leaving Cape Verde as the only country never to have participated.
Ordinarily, Egypt would be among be expected to qualify for the 16-nation tournament and be among the favourites to go on and claim the $1.25 million (1.05 million euros) first prize.
But Morocco present a tough challenge in a home-and-away final round qualifier to be played on successive weekends with Alexandria hosting the first leg and Rabat the return game.
Egypt rely less on Europe-based stars than most African countries with 12 of the 23-man squad that finished 2017 Africa Cup of Nations runners-up playing at home.
However, two of them will not be eligible to play against Morocco having secured contracts abroad.
Goalkeeper Essam El Hadary, who turned 44 during the Cup of Nations in Gabon to become the oldest player in the history of the tournament, has moved to a Saudi Arabian club.
Ahmed Hegazy, a centre-back with a fondness for heading goals off set-pieces, has moved to English Premier League outfit West Bromwich Albion on loan from Al Ahly.
While Egypt can call on a host of experienced international campaigners from Ahly and arch rivals Zamalek, the stars of Raja and Wydad Casablanca and FUS Rabat can boost Morocco.
Title-holders and twice champions the Democratic Republic of Congo travel across the Congo river to face Congo Brazzaville.
Survivors from the team that defeated Mali 3-0 in a 2016 final fought in a Kigali downpour include TP Mazembe striker Meschak Elia.
In a memorable Nations Championship, Elia netted twice in the final to finish leading overall scorer and was voted the best player of the tournament.
Stars from the leading DR Congo clubs dominate the squad with Mazembe supplying eight players, Daring Club Motema Pembe six and V Club four.
The draw kept west African giants Ghana, the Ivory Coast and Nigeria apart and all start with away fixtures.
Ghana have probably the trickiest assignment, against Burkina Faso in Ouagadougou, the Nigerians tackle Benin in Cotonou and the Ivorians face Niger in Niamey.
Uganda, who named local coaches Moses Basena and Fred Kajoba as successors to Serb Milutin Sredojevic, host Rwanda as they seek a fourth consecutive finals appearance.
Clubs refusing to release players have severely hampered the chances of South Africa overcoming Zambia, with the first leg in coastal town East London.
