Abstract: Sweet potato (Ipomoea batatas L.) is one of the most typical cash crops in modern agriculture. However, the conventional manual planting is time-consuming and labor-intensive, leading to high production costs. This study aims to explore the suitable planting density and transplanting depth for the mechanical production of the sweet potato. A two-year field experiment was conducted in Rongchang District of Chongqing City, China (29°40’N, 105°59’E) from 2022 to 2023. The test material was taken from the widely local variety of the sweet potato (Yushu 198). A two-factor split-plot design was adopted for optimization. The plots were set with three planting spacings: 25 cm (P5, 50 025 plants/hm²), 30 cm (P4, 41 688 plants/hm²), and 36 cm (P3, 34 739 plants/hm²). While the subplots were designed with two transplanting depths: 15 cm (D15) and 20 cm (D20). A systematic investigation was then made on the responses of the fresh tuber yield, starch content, soluble sugar content, tuber starch extraction rate, rhizosphere soil nutrients, and soil microbes to the different combinations of the mechanical transplanting depths and densities. The results indicate that there were significant differences in the impact of the mechanical planting density and depth on the sweet potato yield, quality, and rhizosphere soil nutrients. Additionally, an optimal planting range enhanced the mechanical planting density and depth, leading to the high yield of the fresh sweet potato, starch content, and tuber starch extraction rate. There was also an effective increase in the contents of alkaline nitrogen, available phosphorus, available potassium, microbial biomass carbon, microbial biomass nitrogen, microbial biomass phosphorus, and the number of bacteria, fungi, and actinomycetes. Among them, the P5D20 treatment (50 025 plants/hm², 20 cm) achieved the optimal fresh tuber yield and starch extraction rate, which were 37 619.0 kg/hm² and 30.4%, respectively. Compared with the P5D15 treatment (50 025 plants/hm², 15 cm), the P5D20 treatment significantly increased the contents of the alkaline nitrogen, available phosphorus, available potassium, microbial biomass carbon, microbial biomass nitrogen, microbial biomass phosphorus, as well as the quantities of bacteria, fungi and actinomycetes in the rhizosphere soil by 11.9%, 62.2%, 13.9%, 17.4%, 12.2%, 44.9%, 37.4%, 21.2% and 21.5%, respectively. An optimal combination of the indicators was achieved in a mechanized planting density of 50 025 plants/hm² and a transplanting depth of 20 cm. After that, the high yield, better fruit, and soil quality can be obtained in mechanical production. This finding can provide the practical technical support for the mechanical cultivation of the sweet potato. A strong reference can also offer for the homologous varieties of the sweet potato in similar regions.