Coach Sven Vandenbroeck was gifted a win on his debut assignment before home fans with Stoppilla Sunzu putting Zambia ahead on 15 minutes.
Orlando Pirates midfielder Justin Shonga doubled the lead with a stroke of brilliance in the 54th minute.
Guinea Bissau’s Frederic Mendy was gifted by an unlikely Kennedy Mweene error in the 80th minute.
Republican President Edgar Lungu led thousands of fans in cheering the Chipolopolo on at National Heroes Stadium.
It was the first win for Zambia in three Group K matches and pushes the Chipolopolo to four points.
Zambia will play Guinea Bissau on Sunday away in the final of back-to-back matches.