The average temperature in Mole National Park is about 28°c. In December, the average temperature can fall to 26°c, and can rise up to 31°c in March. The dry season usually lasts from November till March, with average temperatures falling as low as 26°c and rising as high as 31°c in March. The rainy season usually lasts from April to October, and the vegetation is lush during this period. Individual temperatures are highest in March and April, sometimes reaching into the 40°s. The dry harmattan winds may blow between December and February, bringing dusty, hazy weather.

The average annual rainfall in Mole National Park is 1,100 mm, decreasing to 1,000 mm in the north of the park. The relative humidity in the Park reaches 90% at night in the rainy season, and falls to about 70% in the afternoons. In the dry season, the figures are 50% and 20% respectively.