Plant resistance against insects mainly depends on nutrient restriction and toxic metabolites, but the relative importance of nutrition and toxins remains elusive. We examined performance, nutrition ingestion, and transcriptome response of the English grain aphid, Sitobion avenae, feeding on resistant Xiaoyan 22 (XY22) and susceptible Xinong 979 (XN979) wheat cultivars. Aphids had lower body weight and fecundity when feeding on XY22 than on XN979, although the phloem sap of XY22 had a higher nutritive quality (in terms of amino acid:sucrose ratio). Aphids feeding on XY22 also had a lower honeydew excretion rate than those on XN979, suggesting that aphids ingested less phloem sap from XY22. The transcriptome data showed 600 differentially expressed genes (DEGs), and 11 of the top 20 KEGG pathways significantly enriched in DEGs were involved in nutrient metabolism. We found 81 DEGs associated with the metabolism of sugars, lipids, and amino acids, 59 of which were significantly downregulated in aphids feeding on XY22. In contrast, there were 18 DEGs related to detoxifying metabolism, namely eight UDP-glucuronosyltransferases, six cytochromes P450 monooxygenases, one glutathione S-transferase, two ATP-binding cassette transporters, and one major facilitator superfamily transporter; 12 of these were upregulated in the aphids feeding on XY22. Our results indicated that both the quantity and quality of phloem nutrition available to aphids are critical for the growth and development of aphids, and the higher resistance of XY22 is mainly due to the reduction in phloem sap ingested by aphids, rather than toxic metabolites.