Host plant resistance is an important component of integrated pest management of the melon fly, Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae). We studied various antixenotic and allelochemical traits in the fruit for 15 varieties/genotypes of watermelon Citrellus lanatus (Thunb.) Matsumara & Nakai (Cucurbitales: Cucurbitaceae) in relation to resistance against B. cucurbitae under field conditions in a hot arid region of India. Results showed significant differences in tested varieties/genotypes in levels of fruit infestation and larval density per fruit. The varieties/genotypes ‘Asahi Yamato’ (12.73%), ‘AHW/BR-16’ (15.10%), and ‘Thar Manak’ (18.27%) were found to be resistant; ‘Durgapura Lal’ (23.03%), ‘Sugar Baby’ (26.67%), ‘AHW/BR-12’ (29.73%), ‘Arka Manik’ (34.15%), ‘Charleston Gray’ (38.70%), ‘AHW-65’ (35.80%), and ‘AHW-19’ (48.97%) were found to be moderately resistant; and ‘IC 582909’ (53.18%), ‘AHW/BR-60’ (55.52%), ‘BSM-1’ (59.10%), ‘AHW/BR-137’ (60.58%), and ‘AHW/BR-9’ (67.37%) were found to be susceptible to fruit fly infestation. Significant positive correlation (r = 0.99; P < 0.01) was observed between percentage fruit infestation and larval density per fruit. Percentage fruit infestation and larval density per fruit were significantly and positively correlated with fruit length (r = 0.57 and 0.55, respectively) and with days to first fruit harvest (r = 0.75 and 0.76, respectively), but negatively correlated with length of ovary pubescence (r = -0.91 and -0.91, respectively), rind hardness (r = -0.86 and -0.87, respectively), and rind thickness (r = -0.77 and -0.75, respectively). Maximum variation in fruit infestation and larval density were explained by length of ovary pubescence (82.5 and 83.6%, respectively) followed by fruit length (4.3 and 3.0%, respectively) and rind thickness (3.2 and 2.0%, respectively). Free amino acid content was lowest in the resistant ‘Asahi Yamato’ and highest in the susceptible ‘BSM-1’, whereas the contents of phenols, tannins, total alkaloids, and flavonoids were highest in resistant and lowest in susceptible varieties/genotypes. Flavonoid and total alkaloid contents explained 88.4 and 92.0%, respectively, of the total variation in fruit fly infestation and in larval density per fruit.