Weeds comprising of annual monocotyledons, dicotyledons and perennial Cyperus rotundus L. (hereafter referred to as nutsedge) are important constraints in maize-wheat production system in India. They can cause yield losses of 25–30% in maize and 10–25% in wheat. Recently, continuous use of selective herbicides has led to an increase of nutsedge and other annual weeds in maize. There is need for a broad-spectrum weed control strategy that includes control of nutsedge in maize. Herbicide mixtures, containing a nutsedge killer partner herbicide may prove to be more effective for this. Imazethapyr among herbicides available in India possesses nutsedge-killing action, but the tolerance of maize to this herbicide, which is usually recommended for application as post-emergence in soybean and groundnut, is variable. We observed dose-dependent selectivity/tolerance of maize to imazethapyr when applied as post-emergence in a previous trial. Imazethapyr’s pre-emergence application may prove more useful in offering selectivity to maize, but is hardly studied. In addition, its residual/carry-over effect may lead to weed control in following wheat crops grown in sequence with maize, economizing production costs of the maize-wheat system. Therefore, this experiment was designed to evaluate the efficacy of imazethapyr against weeds including nutsedge, and its selectivity in maize crops when applied as pre-emergence in tank-mixture with pendimethalin; to compare these tank-mixtures effects with that of the sequential applications of pendimethalin (pre-emergence) and imazethapyr (post-emergence) in maize; and to evaluate their residual actions combined with tillage and crop residue in wheat under a maize- wheat system. The application of pre-emergence tank-mixture of pendimethalin 0.75 kg a.i. ha−1 + imazethapyr 0.050 kg a.i. ha−1 caused significant reductions in densities of broad-leaved (30%), nutsedge (45.2%), grassy (79.7%) and total weeds (49.1%) compared with un-weeded control (UWC) in maize. It reduced total weed dry weight by 58.3% and gave 56.1% higher maize yields than UWC. Among the tillage treatments adopted in the wheat crop, zero tillage (ZT) + residue (R) resulted in 14.0% greater reductions in weed dry weight and 6.9% higher wheat yields than conventional tillage (CT). It increased maize-wheat system productivity by 5.4% and 7%, respectively over CT and ZT without residue. The application of a tank-mixture of pendimethalin + imazethapyr gave 2.9% lower system productivity, but 8.2% higher net returns than the weed-free control, reducing the weed seed bank by 65% at 0–15 cm soil layer in two years. The application of this tank-mixture (in maize), followed by ZT + residue (in wheat) was more remunerative and could lead to better weed control with 25% and 50% lower doses of pendimethalin and imazethapyr, respectively, and 50% reduction in application cost. This practice can be adopted in maize-wheat system under irrigated conditions in the North-western Indo-Gangetic Plains of India, and in similar agro-ecologies of the tropics and sub-tropics. This result can also be applicable to cropping systems like maize – mustard, maize – barley/oat, subject to further evaluation and refinement under field conditions.