A major question facing global rice systems is the extent to which yield and resource use efficiency indicators can be simultaneously optimized to sustainably meet future food demand. However, research approaches for evaluating synergies and tradeoffs among multiple indicators have been limited to date. Using the case study of rice production in Uruguay, we quantified five cropping system performance indicators at the farm-level from 2012 to 2017, covering approximately 40% of national rice area. Results suggest that maximizing performance in oneindicator is associated with tradeoffs for other indicators, with no farm simultaneously ranking as a topperformer (defined as top 10% of farms) across all indicators. The gaps between the average and topperforming farms were largest for agrochemical contamination risk (33%) and smallest for yield (11%). Comparing the groups of top-performing farms within each indicator revealed opportunities for improving system-level performance via synergistic effects between yield and resource use efficiencies, but not between carbon footprint, agrochemical contamination risk, and other indicators. Importantly, synergistic effects were more pronounced for farms at lower compared to higher productivity levels, suggesting less room for ustainability improvements at higher yield levels, unless yields can be further increased without elevated inputs. Important factors to improve the aggregated sustainability index included N fertilizer rate and seeding date. With potential application to rice production systems worldwide, this study highlights an integrated research approach for quantifying synergies and tradeoffs among multiple indicators to understand opportunities for increasing crop yields without negatively impacting resource use efficiency and environmental footprint.