Weeds are the major biotic stress limiting productivity, profitability and sustainability of direct-seeded rice (DSR). Effective weed control determines the success of DSR. Therefore, a field study was undertaken to assess the impacts of potential pre- and post-emergence herbicides in sequence and integrated use of herbicides with other methods on weeds and DSR. Eleven weed control treatments comprising of six combinations of pre- and post-emergence herbicides, two brown manuring, one herbicide with manual weeding, and two control (weed-free check and unweeded control) were evaluated in a randomized complete block design with three replications. Results showed that grassy weeds were most dominant, constituting 66.0–91.8% of total weed dry weight across the treatments. Unit increase in weed density (per m2) and weed dry weight (g/m2) could reduce rice grain yield by 14.5 and 11 kg/ha, respectively. All weed control treatments impacted weed interference, crop growth and yield significantly. Sequential applications of pendimethalin (1.0 kg/ha) as pre-emergence and ready-mixture of penoxsulam + cyhalofop-butyl (130 g/ha) at 25 days after sowing (DAS) significantly reduced weed dry weight by 87.6% at harvest, and was superior to other treatments. This treatment increased rice grain yield (3.92 t/ha) by 378.9% over unweeded control, gross benefit: cost (2.30) by 31.4% over weed-free check, and gave highest overall impact index (1.27) with an economic threshold level of 9.0 weeds/m2, and found to be the best weed control option in DSR. Likewise, brown manuring followed by application of metsulfuron-methyl 10% + chlorimuron-ethyl 10% (20 g/ha Almix) at 40 DAS led to 80.3% reduction in weed dry weight, causing significant improvements in crop growth and grain yield (3.67 t/ha) with 30.3% higher gross benefit: cost over weed-free check, and could become a profitable alternative weed control option in DSR.