The study hinged on the socio-economic analysis of inorganic versus organic practices in Irish potato production in Kisoro District, Uganda. The study comprised of field surveys and desk reviews using materials gathered from various departments at Kisoro District Local Government (KDLG), NGOs, agro inputs dealers, Key Informants (KI) and farming communities. Production per hectare was looked into since it gives a clue to the types of farming systems employed, which determines the use of inorganic amendments. The findings showed that the use of inorganic practices in Kisoro District is associated with immigrant farmers from Rwanda, NGOs and agricultural extension personnel. Actual adoption is determined by farmer income and type of farming—commercial farmers and farmer associations remained active because of financial capability. The high population pressure, the need for more output, intensive cultivation and reduced soil productivity per ha have led to the use of inorganic practices in Irish potato production. The practices face different challenges such as inability to continuous purchase and judicious use of inorganic fertilizers, threats to human and ecosystem (environmental) health that are paving way for traditional organic farming. The latter contains several benefits including good quality potatoes, low health risks to humans and ecosystems and sustained soil fertility.