The reigning African Footballer of the Year struck after 82 minutes against opponents reduced to 10 men by the red-carding of Jorge ‘Bura’ Nogueira midway through the second half in Bissau.
It has been a memorable five days for Mane, who scored the first goal and created the second when Senegal beat Guinea-Bissau 2-0 in Thies near Dakar last Wednesday.
The two victories lifted Senegal, currently the top ranked national team in Africa, to a maximum 12 points from four matches in Group I, and they qualified with two matches to spare.
Senegal complete their schedule between March 22 and 30 by travelling to Congo Brazzaville and hosting eSwatini, and Liverpool manager Jurgen Klopp will probably request that Mane be rested.
Congo have six points, Guinea-Bissau three and eSwatini none in the struggle to qualify with 2002 and 2019 runners-up Senegal.
A win for the Congolese in eSwatini Monday would put them in pole position to reach the finals after missing out on the 2019 tournament in Egypt.
Another Liverpool star who scored was Guinea midfielder Naby Keita, but Ahmat Abdaraman levelled just before half-time for Chad, who forced a 1-1 Group A draw in N’Djamena for their first point.
Guinea top the table with eight points from four matches, but Mali can overtake them by winning in Namibia Tuesday.
– Comoros need one point –
The Comoros, an island nation off the coast of Mozambique with a population of 875,000, moved within one point of reaching the finals for the first time after a 2-1 home win over Kenya.
Serbia-based Ben — full name El Fardou Mohamed Ben Nabouhane — put the Comorans ahead and Cliff Nyakeya equalised before half-time.
French Ligue 2 forward Faiz Mattoir put the home side ahead a second time four minutes into the second half with what proved the match-winning goal.
Boasting an unbeaten record in Group G, the Comoros have eight points, record seven-time African champions Egypt five, Kenya three and Togo one.
Guided by famed French coach Claude le Roy, Togo host Egypt in Lome Tuesday and must win to have any chance of a top-two finish and qualification for the 24-nation tournament.
Meanwhile, Burundi threw Group E wide open through a 3-1 win over Mauritania in Bujumbura with Saido Ntibazonkiza scoring early in each half for the Swallows.
Morocco top the table and are likely to stay there, but only two points separate Mauritania (five), Burundi (four) and the Central African Republic (three) in an intriguing contest for second place.
The Central African Republic host Morocco Tuesday, but will not enjoy home advantage as the match has been moved from Bangui to Cameroonian port city Douala for security reasons.
Matchday 4 qualifying continues Monday with eight fixtures, one of which has Cup of Nations title-holders Algeria defending a 21-match unbeaten record when they play Zimbabwe in Harare.
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