Lemon is a prominent citrus fruit that supports regional economies worldwide. Several agronomic and fruit quality attributes are affected by the rootstock selection, thus its selection is essential for a successful grove. This study aims to compare the agronomic and quality attributes of four lemon cultivars (‘Mikrokarpo Messaras’, ‘Nouvel Athos’, ‘Femminello Commune,’ and ‘Zia gara Bianca’) grafted onto three rootstocks (‘Sour Orange’, ‘Yuma Ponderosa lemon’, and ‘Volkameriana’). The yield and rootstock/scion ratio were estimated along with fruit morphological characteristics (size, equatorial, and polar diameter). Internal fruit quality was also estimated (total soluble solids, total acidity, juiciness, ascorbic acid, total phenols, and total antioxidant activity). ‘Volkameriana’ rootstock stood out among the studied rootstocks, as all grafted lemon varieties increased their productivity. Its combination with the Italian cultivar ‘Femminello Commune’ exhibited enhanced tree vigor and tree yield. For all studied cultivars, the use of ‘Volkameriana’ or ‘Yuma Ponderosa lemon’ rootstocks decreased the total soluble content and total acidity, increased the ascorbic acid content, and did not influence the TSS/TA ratio, total phenols or total antioxidant activity. In conclusion, the vigorous ‘Volkameriana’ and ‘Yuma Ponderosa lemon’ rootstocks are a promising replacement for ‘sour orange’. This research provides valuable insights into the potential use of ‘Yuma Ponderosa lemon’ as a rootstock for lemons, as existing literature is rather limited.