Soil nitrous oxide (N2O) fluxes comprise a significant part of the greenhouse gas emissions of agricultural products but are spatially and temporally variable, due to complex interactions between climate, soil and management variables. This study aimed to identify the main factors that affect N2O emissions under sugarcane, using a multi-site database from field experiments. Greenhouse gas fluxes, soil, climate, and management data were obtained from 13 field trials spanning the 2011–2017 period. We conducted exploratory, descriptive and inferential data analyses in experiments with varying fertiliser and stillage (vinasse) type and rate, and crop residue rates. The most relevant period of high N2O fluxes was the first 46 days after fertiliser application. The results indicate a strong positive correlation of cumulative N2O with nitrogen (N) fertiliser rate, soil fungi community (18S rRNA gene), soil ammonium (NH4+) and nitrate (NO3−); and a moderate negative correlation with amoA genes of ammonia-oxidising archaea (AOA) and soil organic matter content. The regression analysis revealed that easily routinely measured climate and management-related variables explained over 50% of the variation in cumulative N2O emissions, and that additional soil chemical and physical parameters improved the regression fit with an R2 = 0.65. Cross-wavelet analysis indicated significant correlations of N2O fluxes with rainfall and air temperature up to 64 days, associated with temporal lags of 2 to 4 days in some experiments, and presenting a good environmental control over fluxes in general. The nitrogen fertiliser mean emission factors ranged from 0.03 to 1.17% of N applied, with urea and ammonium nitrate plus vinasse producing high emissions, while ammonium sulphate, ammonium nitrate without vinasse, calcium nitrate, and mitigation alternatives (nitrification inhibitors and timing of vinasse application) producing low N2O-EFs. Measurements from multiple sites spanning several cropping seasons were useful for exploring the influence of environmental and management-related variables on soil N2O emissions in sugarcane production, providing support for global warming mitigation strategies, nitrogen management policies, and increased agricultural input efficiency.