The defoliating beetle Mesoplatys ochroptera Stål (Coleoptera: Chrysomelidae) has become a serious pest of the tropical legume Sesbania sesban (L.) Merrill in agroforestry systems in eastern and southern African countries. In this study, 32 accessions of Sesbania spp. collected from eastern and southern Africa were screened for resistance to M. ochroptera at Msekera, Zambia. Two mechanisms of resistance—antixenosis and antibiosis—were indicated in the different accessions. Accessions of Sesbania bispinosa, S. leptocarpa and S. macrantha were found to be more preferred by the insect compared to S. sesban and S. rostrata accessions. Preference of accessions was negatively correlated with leaf-hair density and positively correlated with the number of leaves per seedling and plant height. Under the conditions of eastern Zambia, some accessions of S. sesban from Kenya, Malawi and Ethiopia were found to be comparable to the Zambian accessions in survival, growth and biomass production. Four accessions of S. sesban—Kakamega (ex Kibwezi) and Kisii 2 from Kenya, Zwai 090 from Ethiopia and Rumphi from Malawi—appeared to compensate well for M. ochroptera damage.