The response of greenhouse watermelon to oxygen nanobubble drip irrigation may depend on the dilution level applied, but the treatment level that optimizes individual yield and fruit-quality traits remains unclear. Here, we evaluated a groundwater control (CK) and three oxygen nanobubble dilution treatments (OB₁, 1:0; OB₂, 1:4; OB₃, 1:16) in greenhouse watermelon by combining yield and fruit-quality measurements with fruit transcriptome analysis. Oxygen nanobubble irrigation increased yield by 8.36%-23.65% and improved single-fruit weight and fruit quality relative to CK, but the optimum treatment differed among target traits. OB₁ produced the highest yield and single-fruit weight; in the autumn crop cycle, it also produced the highest ascorbic acid content, 188.71% higher than CK and 14.15%-83.99% higher than the other oxygen treatments. In contrast, OB₂ gave the best flavor-quality response, producing the highest soluble sugar content and sugar-acid ratio; soluble sugar increased by 6.32%-28.44% relative to CK, and OB₂ exceeded OB₁ and OB₃ by 5.38%-20.64%. Fruit RNA-seq identified treatment-associated expression differences among genes annotated to carbon metabolism, transport and signaling, starch and sucrose metabolism, and ascorbate-related redox processes. OB₁ showed expression differences among genes annotated to AsA biosynthesis and recycling, glutathione metabolism, peroxide detoxification, and NADPH supply, whereas OB₂ showed a distinct carbohydrate-related expression profile alongside the highest soluble-sugar content and sugar-acid ratio. Together, the contrasting yield and fruit-quality outcomes were accompanied by distinct fruit-transcriptome profiles across the oxygen nanobubble-water dilution treatments.