Recent decades have seen many changes in agricultural production systems in Nepal, such as increased mechanization for harvesting of major cereal crops, which leaves a large volume of crop residue in the field, increased herbicide application for weed control, and increased adoption of reduced tillage systems. In this study, we compared the effects of tillage, rice residue and weed managements on yield and yield attributes of wheat cultivated under rice-wheat rotation in the Southern Plain (Terai) region of Nepal. The study was conducted during the wheat growing seasons (November through April) of 2013–2014, 2014–2015 and 2015–2016 in Rupandehi district. The experiment was deployed in a split-split plot design with tillage system as main plot [conventional tillage (CT) and zero tillage (ZT)], residue removal management as a sub-plot [whole residue retained (WR), partial residue retained (PR) and no residue retained (NR)], and weed management as a sub-sub plot [(manual weeding (MW) and chemical weeding (CW)], replicated three times. Analysis of variance was applied to the yield and yield attributes of wheat for fixed and interaction effects. Averaged across the years, the CT system (2.4 t ha–1) had significantly higher yield than ZT (2.2 t ha–1) but the difference was not consistent in all study years. While rice residue retention did not influence grain yield in Year1, WR produced greatest and NR produced lowest yield in Year2 and Year3, indicating potential yield increase in wheat following the whole rice residue retention in the long run. Grain yield did not significantly vary with weed management method, suggesting that manual weed control can be as effective as herbicide in weed management in wheat agroecosystem in the Southern Plains (Terai) region of Nepal.