Maize is a major staple food crop in southern Africa and stress tolerant improved varieties have the potential to increase productivity, enhance livelihoods and reduce food insecurity. This study uses big data in refining the geospatial targeting of new drought-tolerant (DT) maize varieties in Malawi, Mozambique, Zambia, and Zimbabwe. Results indicate that more than 1.0 million hectares (Mha) of maize in the study countries is exposed to a seasonal drought frequency exceeding 20% while an additional 1.6 Mha experience a drought occurrence of 10–20%. Spatial modeling indicates that new DT varieties could give a yield advantage of 5–40% over the commercial check variety across drought environments while crop management and input costs are kept equal. Results indicate a huge potential for DT maize seed production and marketing in the study countries. The study demonstrates how big data and analytical tools enhance the targeting and uptake of new agricultural technologies for boosting rural livelihoods, agribusiness development and food security in developing countries.