BACKGROUND: A strong health information system (HIS) is one of the essential building blocks for a resilient health system. The Ministry of Health (MOH) of Ethiopia is working on different initiatives to strengthen the national HIS. Among these is the Capacity-Building and Mentorship Partnership (CBMP) Programme in collaboration with public universities in Ethiopia since November 2017. This study aims to evaluate the outcomes and share experiences of the country in working with universities to strengthen the national HIS. METHODS: The study employed a mixed-methods approach that included 247 health organizations (health offices and facilities) of CBMP-implementing woredas (districts) and 23 key informant interviews. The programme focused on capacity-building and mentoring facilities and woreda health offices. The status of HIS was measured using a connected woreda checklist before and after the intervention. The checklist consists of items related to HIS infrastructure, data quality and administrative use. The organizations were classified as emerging, candidate or model based on the score. The findings were triangulated with qualitative data collected through key informant interviews. RESULTS: The results showed that the overall score of the HIS implementation was 46.3 before and 74.2 after implementation of the programme. The proportion of model organizations increased from 1.2% before to 31.8% after the programme implementation. The health system-university partnership has provided an opportunity for higher education institutions to understand the health system and tune their curricula to address real-world challenges. The partnership brought opportunities to conduct and produce local- and national-level evidence to improve the HIS. Weak ownership, poor responsiveness and poor perceptions of the programme were mentioned as major challenges in programme implementation. CONCLUSION: The overall HIS has shown substantial progress in CBMP implementation woredas. A number of facilities became models in a short period of time after the implementation of the programme. The health system-university partnership was found to be a promising approach to improve the national HIS and to share the on-the-ground experiences with the university academicians. However, weak ownership and poor responsiveness to feedback were the major challenges identified as needing more attention in future programme implementation.