Agriculture forms the cornerstone of food security across sub-Saharan Africa (SSA), serving as a fundamental pillar that sustains livelihoods, supports economic resilience, and underpins regional stability. This region’s population is projected to reach 2.4 billion by the year 2050, which will increase its food demand by 60%. However, recurrent droughts, temperature extremes, and increasing soil salinity are emerging as threats to present and future food security as they restrict agricultural productivity. The biggest challenge facing the SSA region lies in finding ways to adapt its agricultural practices to climate change. This article explores the potential role of extremophile microorganisms in enhancing crop resilience to abiotic stress. Research has so far shown that extremophiles alleviate drought stress in plants by increasing the expression of an array of novel genes, including genes responsible for induced drought, heat and salt stress tolerance, increased production of enzymatic antioxidants, as well as increased production of plant growth promoting phytohormones. Importantly, research shows that (i) extremophile-induced plant growth promotion and stress alleviation is triggered by the presence the stressor (ii) phylogenetically diverse microorganisms isolated from different desert plants can induce stress tolerance in heterologous crop hosts. These findings raise hopes of proofing crops against climate change-induced drought stress and hence ensure food security. However, research on the role of extremophiles in agriculture in the SSA region still lags behind. There is need to build capacity in extremophile agricultural biotechnology in this region, primarily in the form of bioprospecting for isolates exhibiting strong plant growth promoting capabilities.