The aim of this study was to investigate specific management methods for controlling weeds under different climate conditions by reducing the risk of herbicide resistance in maize. Herbicide trials were placed at two locations during 2017 and 2018 and organized in a randomized block design with four replicates of all herbicide combinations (terbuthylazine—pre-emergence and mesotrione post-emergence treatment, terbuthylazine + mesotrione in post-emergence treatment, and terbuthylazine—pre-emergence and dicamba in post-emergence treatment). In the trials, 13 specific weeds were observed. High effectiveness was achieved when using commercial preparations with two active ingredients (terbuthylazine and mesotrione) in both years of research. As the year 2018 featured a higher amount of precipitation, uneven weed sprouting occurred, which resulted in a large number of Setaria glauca (18.50 No m−2), Solanum nigrum (16.50 No m−2), Datura stramonium (13.75 No m−2), and Chenopodium hybridum (10.50 No m−2) plants. Herbicide phytotoxicity was not expressed in maize. Ambrosia artemisiifolia, Solanum nigrum, and Datura stramonium had the highest competitive index (CI 10). The highest maize yield was observed under the application of terbuthylazine + mesotrione in post-emergence (14.223 t/ha). This combination led to the highest weed control costs (35.60 EUR/ha) in 2018, while in 2017, the yield was 12.829 t/ha, with a control cost of 33.99 EUR/ha.