Marigold (Tagetes erecta L.), a crop of significant medicinal, ornamental, and economic value, faces severe industrialization challenges due to weed-induced yield losses (up to 60%). This study aims to identify safe and highly efficient herbicides for marigold, assess their effects on dominant weeds and crop safety, and provide a practical basis for large-scale cultivation. We evaluated 11 pre-emergence herbicides, 13 post-emergence herbicides, and agronomic practices (plastic mulch) through three field trials to optimize weed control, crop safety, and productivity. In Experiment 1, pre-emergence applications of pendimethalin (35% SC) and oxyfluorfen (240 g/L EC) under plastic mulch suppressed 85–99% of grass and broad-leaved weeds, elevating marigold yield to 1655.6 kg/667 m² and increasing lutein content by 10.7% compared to controls, with no phytotoxicity to subsequent wheat (Triticum aestivum L.)or broad beans (Vicia faba L.). Experiment 2 demonstrated that post-cultivation soil treatment with metolachlor · oxyfluorfen · pendimethalin (50% EC) enhanced weed suppression (47.8–53.6%) and yield (3.4% increase) while ensuring crop safety. Experiment 3 revealed that the post-emergence herbicides haloxyfop-P-methyl (108 g/L EC) and fomesafen (250 g/L SL) achieved over 92% reduction in grass weed biomass and over 75% reduction in broadleaf weed density, respectively, alongside a 6.1% yield improvement. Therefore, region-specific strategies are recommended based on local agronomic conditions: high-value production zones should adopt integrated systems combining plastic mulch with pre-emergence herbicides; arid lands with extended crop rotation intervals require pre-emergence herbicides after intertillage and earthing-up; labor-abundant regions can rotate targeted post-emergence herbicides to delay resistance evolution. This study provides data-driven optimization strategies for comprehensive weed management in marigold fields, offering practical solutions to enhance industrial productivity and ecological sustainability.