Climate change causes a shift in the geographical distribution of host pathogens and accelerates plant pathogen evolution. It alters plant diseases’ spread, virulence, and survival between seasons. Whereas plant diseases constitute an important limiting factor to agricultural productivity, the adverse impacts of climate change cut across the globe, with large numbers of poor rural inhabitants who depend on agriculture for survival at greater risk of food insecurity. At the same time, two-thirds of the sub-Saharan African workforce lost their source of livelihood. This chapter explores the measures of safeguarding food security by mitigating the impact of climate change and plant diseases, which could be achieved through conservation agriculture, sustainable soil health management, and employing some innovative approaches. More so, the role of genomics in modern adaptation techniques aids in understanding the plant–microbe interaction and promotes desirable plant traits which were also elucidated, alongside the relevance of sustainable policies. Hence, ameliorating the effect of climate change and plant diseases on food security requires the active participation of researchers, smallholder farmers, and policymakers.