Aboubacar Demba Camara gave Guinea a 21st-minute lead with a shot that went between the legs of a defender and under the body of goalkeeper Jules Goda.
Shoddy defending also contributed to the equaliser 10 minutes later as Guinea goalkeeper Abdoulaye Sylla fumbled a shot and Karl Toko Ekambi netted the rebound.
Francois Kamano snatched the decisive goal on the stroke of half-time by tapping in a cross at the far post.
The result in Molenbeek near Brussels was a surprise as Cameroon won 1-0 last Friday in Tunisia against a team ranked 10 places above Guinea in Africa.
Guinea drew 2-2 with Gabon in France four days ago as numerous African teams took advantage of the FIFA international window to play friendlies.
Countries are preparing for 2019 Africa Cup of Nations qualifiers in June and four rounds of 2018 World Cup qualifiers between August and November.
Egypt, beaten by Cameroon in the Africa Cup of Nations final in Libreville, scored three goals in 15 minutes to overwhelm Togo 3-0 in Alexandria.
Mohamed Elneny of Arsenal completed the scoring midway through the second half for the record seven-time African champions.
South Africa stretched their record unbeaten run to 17 matches in a disappointing 0-0 draw against Angola in Indian Ocean town East London.
Caretaker coach Owen da Gama made nine changes to the team that beat Guinea-Bissau last Saturday with teenage striker Luther Singh given a first cap.
But scoring chances were scarce for the hosts against ultra-defensive opponents playing their second game under new Brazilian coach Roberto Bianchi.
Mozambique and Tanzania both won at home for the second time during the international window.
A stoppage-time goal from Dayo Antonio gave Mozambique a 1-0 win over Lesotho in port city Beira.
Tanzania edged Burundi 2-1 in Dar es Salaam with Mbarak Yussuf snatching the winner 12 minutes from time.
Goals from ‘Gege’ and Julio Tavares within 23 minutes of the kick-off brought Cape Verde a 2-0 victory in Luxembourg.