This study aims to investigate the impact of mechanized operations on flue-cured tobacco production in the tobacco-growing areas of Southern Anhui, identify key factors for the integration of agricultural machinery and agronomic practices in each production stage, and provide a basis for establishing a fully mechanized production system in tobacco production regions. Comparative experiments on mechanized operations were conducted in the Xuancheng tobacco area of Anhui Province for six key stages, including ridge-building, fertilization, transplanting, earthing up, plant protection, and topping and bud inhibition, as well as a fully mechanized trial. The effects of different operation methods on the agronomic traits, economic performance, and labor costs of flue-cured tobacco were analyzed. The results showed that the high-ridge without earthing up technique increased the number of effective leaves, reduced the length and width of middle leaves, improved tobacco yield, output value, and the ratio of middle and high-grade leaves, while reducing labor costs by 71.43%. The integrated ridge-building and fertilization technique increased plant height and the number of effective leaves, enhanced tobacco output value and the proportion of high-grade leaves, and reduced labor costs by 25.23%. Mechanical transplanting had no significant effect on the agronomic traits of tobacco plants but increased tobacco yield and reduced labor costs by 62.96%. A base-to-topdressing ratio of 1:1 was identified as optimal for southern Anhui, contributing to higher tobacco output value and an increased proportion of high-grade leaves. UAV-based plant protection technology promoted leaf length and width, improved tobacco yield and output value, and reduced labor costs by 34.44%. The integrated mechanical topping and bud inhibition technique had limited effects on agronomic traits, maintained stable tobacco yield, and reduced labor costs by 26.66%. Fully mechanized operations had a certain negative impact on the width of upper leaves but generally improved tobacco yield, output value, and the proportion of high-grade leaves, while reducing overall labor costs by 37.66%. In summary, the integration of agricultural machinery and agronomic practices had limited effects on the agronomic traits of flue-cured tobacco but ensured stable yield, with some techniques showing certain promotive effects. The most significant advantage was observed in labor reduction and cost savings, effectively improving work efficiency and substantially lowering comprehensive operational costs.