Background <p>Lupus nephritis remains a severe manifestation of systemic lupus erythematosus across African populations, where diagnostic and therapeutic challenges significantly impact patient outcomes. This systematic review examines the clinical spectrum and management realities of this condition in African settings.</p> Methods <p>Following PRISMA guidelines, we identified seven qualifying studies after screening 662 records from major databases. The analysis included five case reports and two case series documenting confirmed lupus nephritis cases across multiple African regions. We systematically evaluated patient characteristics, diagnostic approaches, treatment regimens, and clinical outcomes using standardized quality assessment tools.</p> Results <p>Seven studies reporting 16 patients from four countries were included. The female-to-male ratio was 14:2 (7:1). Histological classifications included Class IV (5 cases), Class V (4 cases), Class VI (3 cases), and mixed IV/V (1 case), with one case diagnosed clinically. Two patients died and three progressed to end-stage renal disease requiring dialysis. Most cases occurred in young women, commonly presenting with nephrotic syndrome and hypertension. Proliferative and membranous patterns were the predominant biopsy findings. Corticosteroid-based regimens led to improvement in several patients, though outcomes varied regionally, with North African cases showing better responses than those from other regions where late presentation predicted poorer prognosis.</p> Conclusion <p>These findings underscore both the clinical challenges and opportunities in managing lupus nephritis across Africa. The demonstrated variability in outcomes calls for coordinated efforts to establish context-appropriate diagnostic protocols and treatment guidelines, with particular attention to resource-limited settings.</p> Clinical trials <p>Not applicable.</p>