The Ivorians won the last edition on home soil in February and are heavily fancied to be one of the top-two finishers in Group G and book a place at the next tournament.
But they had to turn to substitute striker Jean-Philippe Krasso to ensure success, as he came off the bench in Bouake to net twice in the final 16 minutes.
Friday's round of qualifying matches also saw a win for Morocco, who will host the 2025 finals and are automatically in the 24-team field but still participating in the preliminary competition.
The Democratic Republic of Congo and Egypt were the other former continental champions who got their campaigns off to successful starts.
Egypt, led by Liverpool star Mohamed Salah, made light work in Cairo of the threat of the Cape Verde Islands, who were the surprise package of the last finals, with Rami Rabia and Omar Marmoush netting in the first half and Ibrahim Adel adding a 70th minute effort for a 3-0 success.
Mohamed Salah (L) celebrates after Mohamed Hamdi's (R) goal against Cape Verde. (AP PHOTO)
The Congolese edged Guinea 1-0 in Kinshasa with a first half goal from Watford striker Edo Kayembe.
Four penalties were awarded in the first half of Morocco's 4-1 win over Gabon in Agadir – two converted for the hosts by Hakim Ziyech but Pierre-Emerick Aubameyang had his first effort for Gabon saved before netting a second spot kick 24 minutes later for a 2-1 halftime deficit.
Aubameyang also struck the woodwork but a 59th minute goal from Real Madrid's Brahim Diaz and a late effort from Ayoub El Kaabi ensured a comprehensive 4-1 victory for Morocco.
Sadio Mane's 16th-minute goal handed Senegal the lead in their Group L clash with Burkina Faso. He raced away to score after teammate Nicolas Jackson had stripped the visitors of possession to set Mane away.
But they gave away a late equaliser deep in added time for a 1-1 draw.
In Johannesburg, South Africa kept up their 26-year unbeaten home record in Cup of Nations qualifiers by scoring in the 95th minute for a 2-2 Group K draw with Uganda.
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