BACKGROUND: As more countries progress towards malaria elimination, a better understanding of the most critical health system features for enabling and supporting malaria control and elimination is needed. METHODS: All available health systems data relevant for malaria control were collated from 23 online data repositories. Principal component analysis was used to create domain specific health system performance measures. Multiple regression model selection approaches were used to identify key health systems predictors of progress in malaria control in the 2000-2016 period among 105 countries. Additional analysis was performed within malaria burden groups. RESULTS: There was large heterogeneity in progress in malaria control in the 2000-2016 period. In univariate analysis, several health systems factors displayed a strong positive correlation with reductions in malaria burden between 2000 and 2016. In multivariable models, delivery of routine services and hospital capacity were strongly predictive of reductions in malaria cases, especially in high burden countries. In low-burden countries approaching elimination, primary health center density appeared negatively associated with progress while hospital capacity was positively correlated with eliminating malaria. CONCLUSIONS: The findings presented in this manuscript suggest that strengthening health systems can be an effective strategy for reducing malaria cases, especially in countries with high malaria burden. Potential returns appear particularly high in the area of service delivery.