Climate change is a major global threat triggering extreme weather/climatic events such as droughts and desertification. In Cameroon, anthropogenic climate change has made droughts recurrent and hastened the advancement of desertification southwards into the Sudano-Sahelian and Guinea high savannah regions. The impacts of these environmental hazards are far reaching notably on agriculture, fishing, and livestock keeping sectors. It is in this light that this chapter examines the phenomena of drought and desertification in the era of anthropogenic climate change laying emphasis on the manifestations, impacts, and nature-based adaptation/mitigation options in the Guinea high savannah and Sudano-Sahelian regions of Cameroon. Findings reveal that desertification is mainly affecting the Sahelian zone while droughts are recurrent across the Guinea high savannah and Sudano-Sahelian regions. The impacts of droughts and desertification are mainly adverse with the agriculture, livestock keeping, and fishery sectors bearing the brunt. Nature-based adaptation and mitigation options are increasingly being adopted at household, community, and regional levels with the most common being agroforestry, controlled grazing, protected areas, “Operation Green Sahel,” planted forests, bamboo plantations. Based on the findings uncovered, it is recommended that favorable policies should be crafted and implemented to encourage the adoption of nature-based solutions at household, community, and regional levels as this will go a long way to mitigate droughts and desertification while fostering the fight against climate change through environmental protection and conservation.