The aim of this study was to investigate the efficacy and phytotoxicity of herbicides in combinations and to determine their economic feasibility in the soybean crop. The trials were placed at two locations, Pobeda and Budisava (Serbia), during 2016 and 2018, organized in a randomized block design with four replicates of all herbicide combinations (metribuzin + S-metolachlor; imazamox + oxasulfuron + typhenesulfuron-methyl; metribuzin + S-metolachlor + imazamox + oxasulfuron + typhenesulfuron-methyl; and bentazon + imazamox + typhenesulfuron-methyl). At the first location, 16 weed species were determined, while in the second location, 14 were determined. The highest reduction in the number of weeds was achieved at the first location, using a combination of herbicides metribuzin + S-metolachlor + imazamox + oxasulfuron + typhenesulfuron-methyl with a total efficacy that ranged from 96.98% to 97.40%. Only on the second location bentazone + imazamox + tifensulfuron-methyl showed passable phytotoxicity on soybean, during both years. Based on the established economic justification, in the combinations of metribuzin + S-metolachlor + imazamox + oxasulfuron + typhenesulfuron-methyl, yield was increased for 2350 kg/ha or 1.91 times more, according to the untreated variant at first location. The economic injury level at the most effective combination of herbicides was 52.70 weeds/m 2 .Soybean (Glycine max (L.) Merr.) is a wonder crop of the twentieth-century and an important source of protein and vegetable oil for human and animal consumption. Today, the largest soybean producers of the world are the USA, Brazil, and Argentina [6,7]. The soybean contains approximately 40%-45% protein and 18%-22% oil, and it is a rich source of vitamins and minerals, with a favourable composition of the amino acids. For this reason, soybean is recommended for use in human consumption as a part of cholesterol-free diets [8]. In addition to this, soybean can improve soil fertility by fixing atmospheric nitrogen from the air [9], and its oil is being used for biodiesel [10]. In the semiarid and subhumid regions of the world, water stress is a major factor limiting soybean production [11]. In our country, climate has a great impact on plant growth and development, so light, heat, air, and water often represent limiting factors [12]. Economic feasibility and selection of most effective measures in weed management, during the crop season, can be the key to maximizing yields. Serbia has favorable conditions for growing soybeans though proper cultivation technology, and selection of variety is a prerequisite for economically viable soybean production. In 2016, average soybean yields in Serbia were at the level of world yields average, while production amounted to 576,446.00 t [13].Heavy weed infestations in soybeans highly interfere with the timeliness and efficiency of harvests, and if not controlled, cause severe losses in crops [14]. In soybean production, almost 37% of attainable production is endangered by weed competition compared to pathoge...