A field experiment was undertaken to determine optimum combination of weed management practices and inter-row spacing levels for effective weed control in maize at Bako agricultural research center, Western Oromia, Ethiopia during 2018 main cropping season. The treatments included pre-emergence s-metolachlor 290 g/L + atrazine 370 g/L (1.0, 2.0 and 3.0 L ha-1), hand pulling and hoeing 25 and 45 days after sowing (DAS) and weedy check in combination with inter-row spacing levels (65, 70, 75, and 80 cm). The experiment was laid out in a randomized complete block design with a factorial arrangement in three replications. The experimental field was infested with 22 weed species belonging to 12 families, out of which 77.3 %, 18.2 % and 4.5 % were broad leaved, grass and sedges, respectively. Weed management practices (WMP), inter-row spacing (IRS) and their interaction significantly influenced the weed density, dry weight and weed control efficiency at 25 and 70 DAS. All parameters of the crop were significantly affected by WMP and IRS. However, their interaction was non-significant except for number of ear per plant and grain yield. The highest grain yield was recorded in inter-row spacing of 65 cm treated with hand pulling and hoeing 25 and 45 DAS (10492.0 kg ha-1). Whereas, the lowest grain yield (2237.0 kg ha-1) was obtained from weedy check plot at 80 cm inter-row spacing. On the other hand, maize planted at 65 cm IRS in combination with 2 L ha-1 s-metolachlor 290g/L + atrazine 370 g/L gave comparable grain yield which was statistically at par with that of hand pulling and hoeing 25 and 45 DAS and 3 L ha-1 s-metolachlor 290g/l. + atrazine 370 g/L involving the same IRS. Hence, putting the environmental concern and scarce labor force under consideration, the use of reduced rate (2 L ha-1) of herbicide in combination with narrower IRS would be the best option for effective weed management in maize. Furthermore, integration of narrower IRS with other weed management treatments enhance maize grain yield there by improving weed control efficiency.