In the midwestern United States, especially Missouri, winegrape (Vitis sp.) growers mostly plant interspecific hybrids, which are well adapted to the climate and pests of the region. ‘Chambourcin’ (an interspecific French-American hybrid) is one of the most widely planted winegrape cultivars in the area. It is usually grown as own-rooted (nongrafted) vines because the economic and horticultural benefits of grafting this cultivar to rootstocks have not been well developed. Further, few significant winegrape rootstock evaluations have been conducted in the midwestern United States, including evaluations of newer rootstocks developed and released by private and public breeding programs. The aim of this study was to assess the potential value of using rootstocks in ‘Chambourcin’ production in southern Missouri, with implications for the midwestern United States. Fruit yield, vine growth, and fruit composition metrics from ‘Chambourcin’ on 10 different root systems [own-rooted, and grafted to rootstocks ‘Couderc 3309’, ‘Couderc 1616’, ‘Paulsen 1103’, ‘Sélection Oppenheim 4’, ‘Millardet et de Grasset 420A’, ‘Millardet et de Grasset 101-14’, ‘Kingfisher’, ‘Matador’ (all Vitis sp.), and ‘Gloire de Montpellier’ riverbank grape (Vitis riparia)] in an experimental vineyard in southwest Missouri were compared. Following three establishment years (2008–10), data were collected across four growing and vintage seasons (2011–14). Yield components evaluated included total fruit production, clusters per vine, cluster weight, berry weight, weight of cane prunings, and crop load. Petiole mineral analysis was conducted in 2011, 2013, and 2014. Grape juice attributes measured were soluble solids concentration, juice pH, titratable acidity (TA), potassium (K), anthocyanins, tannins, phenolics, and organic acids. When simply comparing grafted vs. ungrafted vines, grafting generally induced higher plant vigor and a higher pH in the juice, whereas the other parameters did not differ. When the performances were compared among the 10 root systems, vines grafted to ‘Couderc 3309’ had higher yields compared with vines grafted to six other rootstocks and own-rooted vines. Grafting to ‘Millardet et de Grasset 101-14’ induced higher cluster weight compared with the other rootstocks. The ‘Millardet et de Grasset 420A’ rootstock promoted a higher pH and TA as well as a higher concentration of K in the juice, and ‘Paulsen 1103’ also promoted high pH, TA, and malic acid in the juice, and higher concentrations of phosphorous (P) and K in the petiole compared with most rootstocks. ‘Gloire de Montpellier’ induced a lower P content in the petiole and a higher tartaric/malic acid ratio. Rootstock use can strongly influence some vineyard production metrics as well as nutrient uptake and K levels in the juice (the latter further influencing juice pH). The results of this study provide insights into the complex viticultural and enological interactions resulting from the use of rootstocks in hybrid winegrape production in Missouri, USA.