The 2017 winners were made to work hard for their victory in Ismailia, as both goals arrived in a three-minute period in the final half-an-hour of the match.
Yaya Banana broke inexperienced Guinea-Bissau's resolve with a header in the 66th minute and substitute Stephane Bahoken made a swift impact by adding a second.
Guinea-Bissau, competing in the finals for just a second time, struggled to create much over the 90 minutes and relied on Jonas Mendes to keep them on level terms until Cameroon eventually made the breakthrough.
Christian Bassogog fired over with the angle against him from the best of the Indomitable Lions' first-half chances and Mendes got down to his right to push aside Joyskim Dawa's header from the next big opening 29 minutes later.
It looked like it was going to be a frustrating day when Eric Maxim Choupo-Moting was the next to be thwarted by Mendes with his curling effort from outside the box early in the second half, but Banana found a way through just past the hour.
Karl Toko Ekambi sent in the corner and Banana's downward header beat Mendes and covering defender Rudinilson Silva on the line.
And it did not take long for the second goal to arrive, as a headed clearance in the box ricocheted off Sory Mane and fell nicely for Bahoken to sweep home from six yards.
Guinea-Bissau almost pulled one back 18 minutes from time, only for Piqueti Silva's header to hit the frame of the goal.
KEY OPTA FACTS
- Cameroon have lost only one of their last 10 Africa Cup of Nations games (W4 D5), after losing three of their previous five.
- Guinea-Bissau have lost their last three games in the Africa Cup of Nations.
- Cameroon have kept four clean sheets in their last five Africa Cup of Nations games.
- Cameroon's last eight goals in the Africa Cup of Nations have been scored after the 59th minute.
- Banana and Bahoken both scored their first goals in the Africa Cup of Nations with their first shots in the competition.