Abstract: Agricultural production is one of the main sources of anthropogenic greenhouse gas (GHG) emissions, contributing 50% and 60% of CH4 and N2O emissions, respectively. This study evaluated the rice yield and components, the CH4 and N2O emissions and the global warming potential between the triple rice (R-R-R) and sesame-rice rotation (S-R-R) systems in Can Tho city, Vietnam. The experiments were conducted in three cropping seasons: spring-summer 2016, summer-autumn 2016, and winter-spring 2016–2017. The results showed that there was no significant difference in the yield components and grain yield between the triple rice and sesame-rice rotation systems. The application of a sesame rotation in rice-based system could reduce the CH4 and N2O emission by 30.5% and 18.7%, respectively. The global warming potential in the S-R-R rotation was 9 860 kg CO2e/ha, significantly lower than the R-R-R rotation (12 410 kg CO2e/ha) by 20.6%. These results show that the S-R-R rotation has the potential to mitigate the GHG emissions, especially CH4, which contributes a large amount of emissions in the rice cultivation.