Self-care, while not a new concept or term, has received greater attention and relevance during the COVID-19 pandemic as an innovative approach to reduce pressure on strained health systems, empower individuals, and improve health outcomes, particularly for the most vulnerable. Several ministries of health (MOHs) have expressed interest and commitment to scaling up self-care in light of the pandemic and in response to the World Health Organization (WHO) consolidated guideline on self-care interventions for health: sexual and reproductive health and rights (June 2019). This case study summarizes how the Federal Ministry of Health (FMOH) in Nigeria and the MOH in Uganda pioneered national guidelines for self-care in 2020 – among the first national self-care guidelines in the world – as the first step toward adopting self-care as an approach to achieve universal health coverage (UHC).