•Global monitoring of how healthy ecosystems support thriving communities is needed.•Essential Ecosystem Service Variables (EESVs) can track changes in human-nature interactions.•Six complementary EESV classes provide an encompassing picture of these linkages.•Proof-of-concept testing of EESV classes confirms their readiness for monitoring.•EESVs will track progress towards achieving the Sustainable Development Goals. Global frameworks to guide consistent monitoring of changes in human–nature interactions across space and time are needed to better understand how healthy ecosystems support societies and to inform policy design. Monitoring Essential Ecosystem Service Variables (EESVs) can provide a comprehensive picture of how links between nature and people are changing. A first proposed set of EESV classes comprises: ecological supply, anthropogenic contribution, demand, use, instrumental values, and relational values. Development of specific indicators of these classes for three exemplary ecosystem services (food from fisheries, crop pollination and wildlife viewing) confirms their readiness for global operationalization. The EESV classes will advance our ability to monitor progress towards achieving the Sustainable Development Goals.