Neurological disorders are currently among the top causes of disability adjusted life-years (DALYs) and deaths globally. A vast increase in disease burden is projected, particularly in low- and lower middle-income countries (LLMIC). Paradoxically, in LLMIC settings, neurological disorders are often neglected, underdiagnosed, receive insufficient funding, and limited research. To combat the growing burden of disease, increasing focus must be placed on management of neurological disorders. Cost-effectiveness analyses of epilepsy (acute- and long-term management), migraine (first-line treatment, prophylaxis), Parkinson’s disease (drug treatment, physical therapy), and dementia (diagnosis and follow up, drug treatment, caregivers interventions) were performed to inform policy makers in Ethiopia, Malawi, and Tanzania. Health system costs were collected through a top-down microcosting method. Costing and coverage data were collected with expertise of East African neurologists and medical experts. Efficacy estimates were gathered by estimating the mortality or disability reduction, based on meta-analyses or systematic reviews. The cost-effectiveness analyses, calculating the incremental cost-effectiveness ratio (ICER), were conducted with FairChoices: DCP Analytics Tool. The health benefits of the interventions were estimated in DALYs averted. Cost-effectiveness analyses identified the long-term management of epilepsy (ICER: 0.35), self-managed treatment of migraine (ICER: 45.93), and support for dementia caregivers (ICER: 0.0004) as the best-buy interventions. Parkinson’s disease and the other dementia interventions were not deemed cost-effective in resource-constrained settings, because of its high costs or limited individual benefits. However, these interventions can be significantly impactful for patient’s families, indicating the need for further exploration of the non-health benefits using alternate methodology. The current findings support that an impact in managing neurological conditions can be made by scaling-up the identified cost-effective interventions in resource-constrained settings. By including these considerations carefully, a revision of the essential health benefit package can initiate a prime step forward in pursuit of poverty reduction and health equity.