Simple Summary The majority of Carica papaya L. cultivars used in tropical and subtropical areas are classified as susceptible to drought conditions. Irrigation management is a key tool to alleviate scarcity of water resources effects and obtain an acceptable yield in terms of quantity and quality. In this work, we applied a regulated deficit irrigation system in an experimental field using "Intenzza" and "Siluet", characterized by an elevated watering requirement. The results indicated that water stress decreases the total leaf area, being "Intenzza" affected by both severe and moderate stress, while in "Siluet" this reduction was caused especially by severe stress. Water deficit also decreased plant growth but dissimilarly in both genotypes. In addition, while in "Intenzza" moderate and severe stress decreased fruit fresh weight and increased total soluble solutes levels, in "Siluet" only severe stress reduced fresh weight and watering did not alter sugar index. Furthermore, drought only impaired fruit mineral levels in few dates by a little decrease or even a major accumulation of some nutrients compared to control. Overall, the water shortage kept a suitable organoleptic quality at nutritional and total soluble solutes levels in both cultivars, and "Siluet" seems to better tolerate the middle water stress regarding fruiting. The current genotypes of Carica papaya L. cultivated worldwide are considered relatively tolerant or sensitive to drought conditions, depending specifically on the cultivar features and the severity of water shortage. In this work an experimental field was established by subjecting "Intenzza" and "Siluet" to the following water regimes: Control ("CT"), plants irrigated at field capacity (100%); Moderate Deficit Irrigation ("MDI", watered at 66%); and Severe Deficit Irrigation ("SDI", watered at 50%). The results indicated that water deficit decreases leaf number leading to a decline of total leaf area, being "Intenzza" equally affected by "SDI" and "MDI", whereas in "Siluet" the major decrease was induced by "SDI". Regarding fruit development, in "Intenzza", "MDI" and "SDI" did not affect fruit number except two dates (120 and 202 DAT), decreased fruit fresh weight (FW), and increased total soluble solutes (TSS) levels, while in "Siluet" only "SDI" reduced fruit FW and watering systems did not change TSS, suggesting a better performance of this cultivar under "MDI". In addition, drought did not impair fruit mineral concentrations excepting in few dates, and in such cases stressed fruits accumulated a slight minor or even major concentration of some nutrients than control, maintaining consequently suitable organoleptic quality.