Fructans are carbohydrates found in many plants, including wheat (Triticum aestivum L.), and they serve physiological roles in both plants and humans. Genomic selection (GS) could facilitate the rapid development of climate-resilient, nutritionally improved wheat cultivars, such as high-fructan cultivars, while decreasing resourceintensive phenotyping requirements. However, few empirical studies have examined GS for nutritional quality breeding. Although GS can accelerate gain from selection, loss of genetic variation and inbreeding may limit the potential for long-term gain. The objectives of this study were (a) to determine realized gain from GS for wheat grain fructan content with simple truncated selection (TS) and optimized contribution selection (OCS) methods, (b) to determine if gains agree with theoretical expectations, and (c) to compare impacts of selection on inbreeding, genetic variance, and indirect selection on agronomic characteristics. Over 2 yr, two cycles of GS were performed with equal contribution TS and inbreeding-constrained OCS selection. Genomic selection with TS and OCS led to a 25 ± 12% and 34 ± 6.4% increase in wheat grain fructan content, respectively. Although positive gains from selection were observed for both populations, OCS populations exhibited these gains while simultaneously retaining greater genetic variance and lower inbreeding levels relative to TS populations.Selection for wheat grain fructan content did not change plant height but significantly decreased days to heading in OCS populations. In this study, GS effectively improved the nutritional quality of wheat, and OCS controlled the rate of inbreeding.