Balde’s first-half goal was decisive against a Nigeria team packed with in-form attackers, including Serie A leading scorer Victor Osimhen, as Guinea-Bissau moved top of Group A with seven points from three games.
Nigeria remain on course to qualify for the finals in Ivory Coast next January with six points from three matches but the defeat comes after losses to Algeria, Costa Rica and Portugal, the first time in 42 years they have lost four games in a row.
It is also Guinea-Bissau's first win against their powerful west African rivals.
In other early kick-offs on Friday, South Africa let a two-goal lead slip at home to Liberia and had to settle for a 2-2 draw. Burnley forward Lyle Foster scored a brace for the home side but they conceded twice late on.
It means the winners of the reverse fixture in Monrovia on Tuesday will qualify for the finals from three-team Group K, while a draw will leave the pair level on points going into a final game each against World Cup semi-finalists Morocco.
Ivory Coast's Sebastien Haller was on target as they defeated Comoros 3-1, while Democratic Republic of Congo beat Mauritania by the same scoreline.
Simon Msuva scored the only goal as Tanzania won 1-0 at East African rivals Uganda, while Cape Verde were held 0-0 by tiny Eswatini in Praia.
The top two sides in each group qualify for the 24-team continental finals.
