Water scarcity constrains the sustainable development of Chinese agriculture, and deficit irrigation as a new irrigation technology can effectively alleviate the problems of water scarcity and water use inefficiency in agriculture. In this study, the drip irrigation cotton field under film in Xinjiang was taken as the research object. Meta-analysis and machine learning were used to quantitatively analyze the effects of different farm management practices, climate, and soil conditions on cotton yield and water use efficiency under deficit irrigation, to investigate the importance of the effects of different factors on cotton yield and water use efficiency, and to formulate appropriate optimization strategies. The results showed that deficit irrigation significantly increased cotton water use efficiency (7.39%) but decreased cotton yield (−15.00%) compared with full irrigation. All three deficit irrigation levels (80~100% FI, 60~80% FI, and 40~60% FI; FI: full irrigation) showed a significant decrease in cotton yield and a significant increase in water use efficiency. Under deficit irrigation, cotton yield reduction was the smallest and cotton water use efficiency increased the most when planted with one film, two tubes, a six-row cropping pattern, an irrigation frequency ≥10 times, a nitrogen application of 300~400 kg·ha⁻¹, and a crop density ≥240,000 per hectare, and planted with the Xinluzhong series of cotton varieties; deficit irrigation in areas with average annual temperature >10 °C, annual evapotranspiration >2000 mm, annual precipitation <60 mm, and with loam, sandy soil had the least inhibition of cotton yield and the greatest increase in cotton water use efficiency. The results of the random forest showed that the irrigation amount and nitrogen application had the greatest influence on cotton yield and water use efficiency. Rational irrigation based on optimal management practices under conditions of irrigation not less than 90% FI is expected to achieve a win–win situation for both cotton yield and water use efficiency. The above results can provide the best strategy for deficit irrigation and efficient water use in drip irrigation cotton under film in arid areas.