Field experiments were conducted in 11 major winter rapeseed producing counties （cities， districts） in Guizhou Province for two consecutive years from 2018 to 2019 and 2019 to 2020 to optimize the models of fertilizer and pesticide for winter rapeseed with direct seeding in Karst mountainous areas of Guizhou Province. The effects of different models of fertilizer and pesticide including the traditional model of fertilizer and pesticide （T1）， the optimized model of fertilizer and pesticide （T2）， no fertilizer application under the optimized model of fertilizer and pesticide （T3）， and no pesticide spraying under the optimized model of fertilizer and pesticide （T4） on the yield and economic benefits of winter rapeseed with direct seeding were studied. The techniques with high-yield and efficient fertilizer and pesticide suitable for winter rapeseed with direct seeding in Karst mountainous areas of Guizhou Province were explored. The results showed that the total nutrient input of T2 decreased by 19.9% and the pesticide input decreased by 69.5% compared with that of T1. The plant height， stem diameter， effective number of branches per shoot， pod length， pod density of winter rapeseed with direct seeding under T2 was lower than that under T1， with a decrease of 9.8%， 26.4%，10.9%， 10.2%， 24.2% from 2018 to 2019， and 9.5%， 28.3%， 12.8%， 10.9% and 23.9%， from 2019 to 2020. T2 had an advantage of population with a significant increase in harvest density of 199.0% and 194.2%in two consecutive years compared to T1. In two consecutive years， the yield of winter rapeseed under T2 was 2 224.4 kg/hm² and 2 103.3 kg/hm²， increasing by 204.0 kg/hm² and 74.3 kg/hm² compared to that under T1. The utilization efficiency of fertilizer and control efficiency of pesticide under T2 was 2.20 kg/kg， 2.14 kg/kg and 141.82 kg/kg， 106.23 kg/kg， significantly higher than that under T1. The total output value and net benefit of winter rapeseed in two consecutive years under T2 was 11 121.8 yuan/hm²， 10 516.4 yuan/hm² and 5 286.8 yuan/hm²， 4 681.4 yuan/hm²， an increase of 1 020.0 yuan/hm²， 371.6 yuan/hm²， 26 285.0 yuan/hm² and 1 976.6 yuan/hm compared to that under T1， achieving cost savings and income increase. It is indicated that the optimized model of fertilizer and pesticide （T2） can meet the requirements for the growth of winter rapeseed with direct seeding in Karst mountainous areas of Guizhou Province， effectively improving the yield， the utilization efficiency of fertilizer and pesticide， and the economic benefits of winter rapeseed. This optimized model of fertilizer and pesticide （T2） can be promoted and applied as the main promotion model for the production of winter rapeseed with direct seeding in Karst mountainous areas of Guizhou Province.