Conservational tillage (CT) in combination with broad spectrum herbicide may be more efficient and economical in controlling weeds, reducing cost of cultivation, and enhancing wheat yield. Field experiments were carried out to evaluate the effect of tillage and herbicides on weeds and wheat yield under rice-wheat cropping system (RWCS). The results indicated that broad spectrum herbicides particularly, carfentrazone ethyl ester + isoproturon (Affinity 50 WDG) reduced weeds density by 93 and 95% compared to control and also produced the maximum grain yield (6 818 and 6 996 kg ha-1) and HI (harvest index, 44.7 and 44.6%) in 2007-2008 and 2008-2009 growing seasons, respectively. The maximum weeds infestation and the lowest yield were recorded in control. Tillage methods significantly influenced grain yield and HI, while no significant effect on all other parameters. The overall mean yield was significantly higher in zero tillage (5 575 kg ha-1) and reduced tillage (5 584 kg ha-1) compared to CT (5 479 kg ha-1). Besides increasing wheat yield, Affinity 50 WDG and zero tillage are important weed management practices that can be integrated into wheat production in RWCS. However, in case of perennial weeds or insect pests’ infestation, CT in combination with Affinity 50 WDG would be more productive than conservation tillage.