Treatment and reuse of flowback and produced water (FPW) from shale gas extraction for agricultural irrigation has often been proposed as a sustainable alternative to disposal via deep-well injection. Here, we investigate the effects of FPW on the germination period, macroscopic growth, element enrichment, and grain gene expression of wheat upon dilution and advanced membrane treatment of the liquid stream. Compared to tap water, irrigation with treated FPW shortened the germination time, slightly improved the seed vigor index, and ensured a similar germination rate. On the other hand, the biomass and grain yield of mature wheat irrigated with treated FPW and with FPW diluted to 5% groups decreased compared to tests using tap water. After a whole growth cycle of wheat, higher concentrations of nutrients, such as K, Ca, and Mg were enriched in mature wheat tissue irrigated with treated FPW. However, the Pb and Cr contents of mature wheat grains treated with three types of irrigation waters exceeded the standard to varying degrees. A total of 1973 differentially expressed genes were mainly related to binding, catalytic activity, cellular process, metabolic process, and cell part, more than half of which were upregulated and induced by irrigation with treated FPW. These findings provide critical guidance for the reuse of treated shale gas FPW for agricultural application from the perspective of plant uptake of toxic elements, as well as crop and human health risks.