The world has been facing a pandemic owing to COVID-19. We have also seen the geographic expansion and outbreaks of other emerging infectious diseases (EID) in recent years. This paper investigates the direct and indirect effects of land use land cover change (LULCC) on EID outbreaks in the context of Wayanad District of Kerala, India. Wayanad is in the vulnerable tropical forested region, and it is named as one of the four environmental change hotspots. The focus of this project is mainly three EIDs prevalent in this region: Kyasanur forest disease (KFD), Dengue and Leptospirosis. Our results, based on topographical map, remote sensing and extensive field work, show that the natural forest in Wayanad was replaced with agriculture and forest plantation during 1950–2018. This paper further suggests that encroachment of forest by forest plantation causes the human–animal conflict resulting in the outbreak of KFD cases. Our analysis reveals that a high number of Dengue cases is found in the forested regions of the district and over the adjacent human-made agriculture plantation areas. High and medium number of Leptospirosis cases contain a high portion of land area devoted to paddy cultivation and agricultural plantation. In summary, the results clearly show the linkage between the outbreak of above mentioned EIDs and LULCC in the context of Wayanad district, Kerala. We also discuss in detail the causal pathway involving human–environmental dynamics through which plantation leads to the outbreak of KFD. Replacing forests with plantations poses an alarming threat of disease outbreak in the community.