Cassava is an important food and energy crop; however, its cultivation impacts on soil greenhouse gas (GHG) emissions and on soil organic carbon (SOC) remain scarce. This study, conducted in Cambodia, quantified the long-term effects of cassava-based cropping systems on nitrous oxide (N2O) emissions and on SOC sequestration. Established in 2009, the experiment comprised 3 treatments: (1) mono-cropping cassava under conventional tillage (CTM–Cs); (2) mono-cropping cassava under no-tillage with biomass retention (NTM–Cs); and (3) bi-annual rotation of cassava with maize under no-tillage with cover crops use (NTR), where cassava (NTR–Cs) and maize (NTR–Mz) are grown annually. Soil N2O emissions were measured over 2 years (April 2022-24). SOC stocks at equivalent soil mass were measured in 2011 and 2021 using a diachronic approach. The net GHG balance was then calculated. Mean cumulative N2O emissions of the cassava treatments (CTM–Cs, NTM–Cs, and NTR–Cs) varied from 0.74 to 0.87 kg N2O-N ha–1 yr–1 but was significantly lower than cumulative N2O emissions of NTR–Mz (1.42 kg N2O-N ha–1 yr–1). Cassava tuber yield was similar between NTM–Cs and CTM–Cs, while the yield of NTR–Cs was at least 17% higher than CTM–Cs. Considering the trade-off between N2O emissions and SOC accumulation, conservation agriculture systems largely contributed to global warming mitigation by removing -2.40 to -3.58 Mg CO2-e ha–1 yr–1. Our findings highlight the potential of conservation agriculture systems as sustainable practices for food security and climate change mitigation.