In arid desert regions of northwest China, reclamation and subsequent irrigated cultivation have become effective ways to prevent desertification, expand arable croplands, and develop sustainable agricultural production. Improvement in soil texture and fertility is crucial to high soil quality and stable crop yield. However, knowledge on the long-term effects of the conversion of desert lands into arable croplands is very limited. To address this problem, we conducted this study in an arid desert region of northwest China to understand the changes in soil physical-chemical properties after 0, 2, 5, 10, 17, and 24 years of cultivation. Our results showed that silt and clay contents at the 17-year-old sites increased 17.5 and 152.3 folds, respectively, compared with that at the 0-year-old sites. The soil aggregate size fraction and its stability exhibited an exponential growth trend with increasing cultivation ages, but no significant change was found for the proportion of soil macroaggregates (>5.00 mm) during the 17 years of cultivation. The soil organic carbon (SOC) content at the 24-year-old sites was 6.86 g/kg and increased 8.8 folds compared with that at the 0-year-old sites. The total (or available) nitrogen, phosphorus, and potassium contents showed significant increasing trends and reached higher values after 17 (or 24) years of cultivation. Changes in soil physical-chemical properties successively experienced slow, rapid, and stable development stages, but some key properties (such as soil aggregate stability and SOC) were still too low to meet the sustainable agricultural production. The results of this long-term study indicated that reasonable agricultural management, such as expanding no-tillage land area, reting straw to the fields, applying organic fertilizer, reducing chemical fertilizer application, and carrying out soil testing for formula fertilization, is urgently needed in arid desert regions.