Already assured of their place in the last 16, the Super Eagles moved into the knockouts as Group D winners with a 100 per cent record after making it three wins from three.
Umar Sadiq broke the deadlock with his first international goal in the 56th minute, given the simple task of tapping in a superb low cross from Kelechi Iheanacho, who moments earlier had forced Guinea-Bissau goalkeeper Maurice Gomis to turn over the crossbar with an audacious effort from more than 40 yards.
Captain William Troost-Ekong made sure of victory 15 minutes from time, prodding into an empty net on the rebound after the excellent Moses Simon had jinked past several defenders and rattled the bar with a fierce strike.
Troost-Ekong looked to have been denied by the offside flag, but a lengthy VAR review concluded with the award of a goal that put the game beyond doubt.
Guinea-Bissau rarely threatened a response, and head home having failed to score for a competition record seventh consecutive AFCON game.