A long-term high-saline soil environment will limit the improvement of soil quality and cotton yield. Modified tillage management measures can improve soil quality, and the establishment of a soil quality evaluation system will facilitate evaluation of the soil quality and land production potential in southern Xinjiang. The objective of this study was to determine the effects of different tillage management methods on soil quality in saline cotton fields in southern Xinjiang. A three-year experiment was conducted in Tumushuke, Xinjiang, with different deep vertical rotary tillage depths (DTM20, 20 cm; DTM40, 40 cm; DTM60, 60 cm) and conventional tillage (CTM, 20 cm). The soil quality index (SQI) under different tillage management methods was established by using the full dataset (TDS) with a scoring function for eight indicators, including physicochemical properties of the soil from 0 to 60 cm, to evaluate its impact on the soil quality of the saline farmland in southern Xinjiang. The results of the study showed that deep vertical rotary tillage management can effectively optimize soil structure; reduce soil bulk density (BD), soil solution conductivity (EC), and pH; and promote the accumulation of soil organic carbon (SOC) and total nitrogen (TN) in the soil. However, the average diameter of soil water-stable aggregates (MWD) in a 0–60 cm layer becomes smaller with an increasing depth of tillage. This does not reduce crop yields but does promote soil saline leaching. In addition, the significant linear relationship (p < 0.001) between seed cotton yield and soil quality indicated that improving soil quality was favorable for crop yield. The principal component analysis revealed BD, MWD, pH, and EC as limiting sensitive indicators for seed cotton yield, while SOC and TN were positive sensitive indicators. The soil quality index (SQI) values of DT40 and DTM60 were significantly higher than that of CTM by 11.02% and 15.27%, respectively. Overall, the results show that DTM60 is the most suitable tillage strategy to improve soil quality and seed cotton yield in this area, and this approach will provide a reliable theoretical basis for the improvement of saline farmland.