Background Access to life-saving medicines for maternal health remains a major challenge in numerous developing nations. Periodic and continuous assessment of access to lifesaving commodities is of enormous importance to measure progress and ensure sustainable supply. This study aimed to assess the availability and affordability of priority lifesaving maternal medicines in Addis Ababa in January 2021. Methods An institutional-based cross-sectional study design was employed to assess 33 representative private pharmacies, public health facilities, NGO and private hospitals providing maternal health care and dispensing medicines from January 12 to 27, 2021 in Addis Ababa, the capital city of Ethiopia. WHO and Health Action International procedures were followed to determine sample size, sampling of health facilities, and data collection. WHO and UNFPA priority lifesaving maternal health medicines included in the Ethiopia essential medicine list were included in the study. Data were cleaned and entered into SPSS version 25 for analysis. Result The overall mean availability of maternal health medicines was fairly high, 59% (range 6%-94%), as per the WHO availability index. Among the four sectors, the private pharmacy had the lowest availability (40%), while the mean availability in private hospitals, public and NGO/mission sector facilities were 70%, 72% and 72% respectively. Medicines used only for the management of maternal health conditions had lower availability (47%) compared to commodities used for the broader indication (65%). Compared based on source, the average availability of maternal health medicines which could be sourced locally was (68%) higher than imported medicines (55%). Affordability was not an issue in the public sector, public facilities offered maternal health medicines at no cost to the client. On the other hand, the private hospitals dispensed only 13% of the medicines at affordable prices followed by the private pharmacies (17%) and NGO/Mission facilities (29%). Furthermore, key challenges to access maternal health medicines were frequent stockouts in the public sector and the high cost of medicines in the private sector. Conclusion Even though it was below the recommended 80% availability, fairly high availability with variabilities across sectors was observed. Except in the public sector, maternal health medicines were unaffordable in Addis Ababa.