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Hybrid wheat breeding programs need to use chemical hybridizing agents for seed production due to its simplicity. Alternative methods such as cytoplasmic systems or hand pollinations restrict genetic combinations or seed production which limits testing experimental hybrids in large-scale multi-environment trials (METs). Using F2 seed instead of F1 can allow programs to test hybrid cross combinations in METs and the data can be used to supplement selection decisions at early stages of breeding cycle. To test this hypothesis, two METs consisting of 40 entries were conducted in 2017 and 2018 in six locations across Texas and Nebraska. The entries included hybrids at the F2 stage and their respective parents, selected from a previous preliminary F1 evaluation experiment. In six out of 10 test environments, a F2 hybrid had statistically significant higher yield than highest yielding parent. The F2 mid-parent heterosis ranged from − 20.97 to 27.52% in 2017 and − 9.90 to 9.17% in 2018. The F2 high-parent heterosis ranged from − 21.07 to 17.85% in 2017 and − 16.57 to 6.68% in 2018. The heterosis estimates of these cross combinations at F1 stage were extracted from previous large scale METs conducted on nine environments across Nebraska and Texas in 2016–2017. A comparison of F2 heterosis from this study and F1 heterosis from the previous study revealed that F2 heterosis was highly indicative of superior F1 performance. The results provide strong evidence for utility of F2 yield data in selecting superior F1 hybrids. In addition, a practical framework for using F2 performance to aid selecting F1's in a hybrid wheat-breeding pipeline is provided. [ABSTRACT FROM AUTHOR]