The popularity of Vaccinium corymbosum blueberry cv. has increased over time because its fruits are highly valued for their taste, aroma, and multiple ways of use. A field trial with two genotypes and their hybrids was organized during 2021−2022 at the Research Institute for Fruit Growing Pitesti-Maracineni, Romania. This paper proposes a comparative analysis of the quality of berries in 17 hybrids of the 'Simultan' and 'Duke' cultivars, selected by the size and the soluble solid content, in agreement with the objectives of the blueberry breeding program. The genotype influence on berry weight, total soluble solids, pH, vitamin C, total polyphenols, total flavonoids, total anthocyanins, lycopene, β-carotene, and antioxidant activity was determined considering the climatic factors. The results showed that fruit weight varied between 1.22 and 2.47 g, total soluble solids reached a maximum of 19.22 °Brix, and the pH oscillated between 3.14 and 3.89. Vitamin C content varied from 9.52 to 18.69 mg in 100 g fresh weight, with an average of 14.35 mg/100 g. Total polyphenol, flavonoid, and anthocyanin contents averaged 709.92 mg gallic acid equivalent in 100 g fresh weight, 165.48 mg catechin equivalent in 100 g fresh weight, and 81.88 mg cyanidin-3-O-glucoside equivalent in 100 g fresh weight, respectively. Results show that the strategy of growers to produce blueberries with a large diameter, visually attractive for traders and consumers, is not sufficient for repeat sales. Our study proves that large fruits do not have the highest content of bioactive compounds. Smaller berries had higher polyphenol, lycopene, and β-carotene contents. It is recommended that the selection of the hybrid in the breeding program also takes into account the content of bioactive compounds.