Flue-cured tobacco production in Malawi is constrained by both soil-borne (root-knot nematodes and Granville wilt) and aerial borne (angular leaf spot and alternaria brown spot) diseases. To address these multiple challenges, a breeding programme was initiated in 2011/2012 season to develop F₁ hybrids possessing multiple disease resistant and high yielding traits. In 2014/2015 and 2015/2016 season, six F₁ hybrids and three checks were evaluated for disease resistance, cured leaf yield (kg/ha) and quality at five sites in Malawi. A randomised complete block design with three replications was used. Data was collected on disease reaction, yield and quality. Highly significant differences were observed for root-knot nematodes reaction across sites. The test hybrids, HMR09-24 and HMR09-27 were comparable to a nematode resistant check, KRK 26, in terms of nematode resistance but better than the local check, AFH4. The hybrids showed susceptibility to Granville wilt with variable levels as compared to the resistant check, PVH 2110. No significant differences were observed for angular leaf spot, all test lines gave low scores. HMR09-25, HMR09-29 and HMR09-28 produced higher cured leaf yields and compared well with the recommended local checks. No significant variations were observed among the treatments on quality as reflected in the cured leaf colour distribution. Based on two year results, HMR09-29, HMR09-27 and HMR09-26 emerged as better hybrids in terms of combined disease resistance to root-knot nematodes and angular leaf spot while giving better yield and cured leaf quality.