In this study, 21 synthetic hexaploid wheat samples were analyzed and compared for phenolic content (the Folin–Ciocalteu method), phenolic compositions, and antioxidant activity (DPPH, ABTS, and CUPRAC). The aim of the study was to determine the phenolic content and antioxidant activity of synthetic wheat lines developed fromAe. Tauschii, which has a wide genetic diversity, to be used in breeding programs for developing new varieties with better nutritional properties. Bound, free, and total phenolic contents (TPCs) of wheat samples were determined as 145.38–258.55 mg GAE/100 g wheat, 188.19–369.38 mg GAE/100 g wheat, and 333.58–576.93 mg GAE/100 g wheat, respectively. Phenolic compositions were detected by the HPLC system. Gallic acid was found in the highest concentrations in free fractions, whereas gallic, p-coumaric acid, and chlorogenic acid were generally found in the highest concentrations in bound fractions of the synthetic hexaploid wheat samples. The antioxidant activities (AA%) of the wheat samples were evaluated by the DPPH assay. AA% in the free extracts of the synthetic red wheat samples ranged from 33.0% to 40.5%, and AA% values in the bound extracts of the synthetic hexaploid wheat samples varied between 34.4% and 50.6%. ABTS and CUPRAC analyses were also used to measure antioxidant activities. The ABTS values of the free and bound extracts and total ABTS values of the synthetic wheat samples ranged from 27.31 to 123.18, 61.65 to 263.23, and 93.94 to 308.07 mg TE/100 g, respectively. The corresponding CUPRAC values of the synthetic wheats were between 25.78–160.94, 75.35–308.13, and 107.51–364.79 mg TE/100 g. This study revealed that synthetic hexaploid wheat samples are valuable resources for breeding programs for developing new wheat varieties with higher concentrations and better compositions of health-beneficial phytochemicals. The samples w1 (Ukr.-Od. 1530.94/Ae. squarrosa(629)), w18 (Ukr.-Od. 1530.94/Ae. squarrosa(1027)), and w20 (Ukr.-Od. 1530.94/Ae. squarrosa(392)) can be used as a genetic resource in breeding programs to enhance the nutritional quality of wheat.