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Summary Objective To estimate the burden of HIV neurocognitive impairment (NCI) among adult patients on and off antiretroviral therapy (ART) in Sub-Saharan Africa. Methods Estimates were derived from a random effects meta-analysis of prospective studies reporting HIV status, utilization of ART, and the presence of NCI determined using the International HIV Dementia Scale. Results Sixteen studies with quality data from seven countries in Sub-Saharan Africa up to June 2012 were included. Among HIV patients, the frequency of NCI pre-ART was 42.37% (95% confidence interval (CI) 32.18–52.56%), and among those on ART for ≥6 months was 30.39% (95% CI 13.17–47.61%). Respective NCI estimates in studies from Uganda were 46.49% (95% CI 30.62–62.37%) and 28.50% (95% CI −1.31–58.30%). NCI was more common among patients with a concomitant psychiatric ailment. HIV-positive patients compared to HIV-negative controls were predisposed to NCI (odds ratio (OR) 6.49, 95% CI 1.68–25.08); the estimated unadjusted attributable risk of HIV infection leading to NCI was 85%. Meta-regression showed no associations between age, gender, CD4 cell counts, or years of education with NCI. Patients on ART were less likely to have NCI compared to HIV-infected pre-ART patients, with OR 0.36 (95% CI 0.19–0.69). In longitudinal studies with the same patients followed before and at ≥6 months after ART, the OR of NCI after ART compared to pre-ART was 0.23 (95% CI 0.14–0.37). The combined burden of NCI among pre-ART and on-ART patients in Sub-Saharan Africa was estimated at 8 121 910 (95% CI 5 772 140–10 471 680). No publication bias was observed, although residual confounding from differing environmental factors, stages of HIV infection, and viral clades might be a limitation. Conclusions HIV strongly predisposes to NCI leading to a huge burden in Sub-Saharan Africa, and scale-up of ART can substantially reduce it.