In order to identify safe and efficient foliar herbicides suitable for cotton fields in Hubei Province, the effect and safety of 9 herbicides on weed control and cotton yield were compared and analyzed in this study by directional spray of stems and leaves after seedling. The results showed that 21 days after treatments, the control effect of 30% topramezone SC 27 ga.i./hm², 5% imazethapyr AS 100 ga.i./hm², 21% glufosinate-P-ammonium SL 820 ga.i./hm², 51% flumioxazin WG 60 ga.i./hm² and 50% prometryn WP 1050 ga.i./hm² on total grass fresh weight in cotton field were 99.40%, 86.07%, 91.17%, 98.81% and 99.34%, respectively. It was significantly higher than 25% sulfonsulfuron WG 26 ga.i./hm², 15% nitrone SC 190 ga.i./hm² and 10% pyrisulfuron WP 30 ga.i./hm². Yield analysis indicated that all herbicide treatments significantly increased the yield of ‘Gangmian 13’ cotton, with 21% glufosinate-P-ammonium SL 820 ga.i./hm² and 51% flumioxazin WG 60 ga.i./hm², showing the greatest yield increase. Safety evaluation revealed that only 15% mesotrione SC 190 ga.i./hm² posed potential risks to cotton, manifested as a significant reduction in root diameter. Field demonstration (compared to manual weeding) confirmed that both 21% glufosinate-P-ammonium SL 820 ga.i./hm² and flumioxazin WG 60 ga.i./hm² enhanced the yield of ‘Gangmian 13’. In conclusion, 21% glufosinate-P SL and 51% flumioxazin WG applied via directional foliar spraying at tested rates are recommended for weed control in cotton fields. This approach delivers significant efficacy while maintaining crop safety.