Abstract: To explore the weed control efficacy and crop safety of different pre-emergent herbicide combinations in soybean and maize intercropping fields, seven herbicide mixture combinations were screened through pot experiments and field efficacy trials. The combinations include pyroxasulfone + metribuzin/ thifensulfuron-methyl/ flumioxazin/ flumetsulam/ and S-metolachlor + thifensulfuron-methyl/ flumioxazin/ flumetsulam. The results of the pot experiment showed that the seven herbicide combinations exhibited no significant inhibitory effects on the emergence or growth of soybean and maize, nor did they cause irreversible phytotoxicity. Field trials showed that at 20 days after herbicide application, no herbicide injury was observed in soybeans or maize. By 50 days, the combinations of 40% pyroxasulfone SC + 480 g/L metribuzin SC (180 + 432 g a.i./hm²), 40% pyroxasulfone SC + 80% flumetsulam WG (180 + 60 g a.i./hm²), and 960 g/L S-metolachlor EC + 80% flumetsulam WG (1296 + 60 g a.i./hm²) provided 82.21%-89.28% control based on the total weed counts and 89.42%-91.11% control based on the total fresh weight. The overall control efficacy of these three combinations on weeds is better than that of other treatment groups. They are recommended for pre-emergence weed control in soybean and maize intercropping systems, particularly in fields infested with a mixture of gramineous weeds, broad-leaved weeds, and sedge weeds. Compared to control, all herbicide treatments increased the yield of soybean and maize by 11.23%-22.91% and 10.41%-20.25%, respectively.