The quartet of Ibrahim Fuseini, Isaac Botsio, Edwin Gadayi and Abdul Rasheed Saminu beat off stiff competition from rivals Nigeria to win the race.
Team Ghana recorded a time of 8.63 seconds, narrowly beating Nigeria, who ran 38.84 seconds, to the finish line.
This comes after Nigeria beat Ghana to the gold medal during the 4x100m relay final at the 2023 African Games earlier this year.
However, Ghana’s relay team has since beaten their West African rivals three times at different competitions.
Team Ghana emerged victorious at the Bahamas World Athletics Relays, which effectively guaranteed their place at the 2024 Olympics in Paris, with Nigeria settling for silver.
The two countries went head-to-head again in the semi-finals of the African Athletics Seniors Championships, which Ghana won, before once again beating their rivals in the final.
Meanwhile, Ghana’s women's 4×100m relay team have also won silver at the African Athletics Seniors Championships in Douala.
Ghana was represented by Hor Halutie, with Mary Boakye, Deborah Acheampong and Anita Afrifa, who recorded a time of 43.62 seconds.
Earlier, high jumper Rose Amoanimaa also won a gold medal in the women’s high jump at the Championships after scaling a height of 1.87m.
Amoanimaa is currently the best female high jumper on the continent, having also won gold at the African Games three months ago, and will be representing Ghana at the Olympics too.