Currently, growers and winemakers of cold climate interspecific hybrid grape (CCIHG) cultivars rely solely on technological maturity variables of Brix, titratable acidity (TA), and pH as ripening indicators for harvesting and winemaking decisions. In contrast, the use of additional chemical variables to determine optimal harvest times is a common practice in most regions of the world where the European V. vinifera grape is cultivated. As there are significant differences in berry chemistry between CCIHG and V. vinifera, the objective of the present study was to evaluate, by linear regression coupled with PCA and cluster analysis, the suitability of six additional maturity variables (berry fresh weight, total protein, total phenolics, monomeric anthocyanins, percent polymeric color, and total tannins) as potential ripening indicators for the CCIHG cultivars Brianna, Frontenac, La Crescent, Leon Millot, Marechal Foch, Marquette, MN 1220, and Petite Pearl. We observed that berry fresh weight, total phenolics, and percent polymeric color had inconsistent and poorly modelable relationships from year to year and across distinct grape cluster microclimate treatments, resulting in their poor suitability as ripening indicators. In addition to the standard technological maturity variables of Brix, TA, and pH, the variables of total protein concentration for white cultivars and monomeric anthocyanin, total protein, and total tannin concentrations for red cultivars have consistent modelable linear relationships from veraison to harvest, making them good candidates for consideration for future use as ripening indicators.