Expression divergence caused by the genetic variations and crosstalks among subgenomes of the allohexaploid bread wheat (Triticum aestivum. L., BBAADD) is hypothesized to increase its adaptability and/or plasticity. However, the molecular basis of expression divergence remain unclear. Squamosa promoter binding protein-like (SPL) transcription factors are critical for a wide array of biological processes. Here, we constructed expression regulatory networks by combining DAP-seq for 40 SPLs, ATAC-seq and RNA-seq. A group of low-affinity SPL binding regions (SBRs) were identfied to be targeted by diverse SPLs, and caused by different sequence prefrences around the core GTAC motif. The SBRs including the low-affinity ones are evolutionary conserved, enriched GWAS signals related to important agricultral traits. However, those SBRs are highly diversed among the cis-regulatory regions (CREs) from syntenic genes with less than 8% SBRs co-exist in triads genes, suggesting CRE variations are critical for subgenome differentiations. Knocking out of TaSPL7A/B/D and TaSPL15A/B/D sub-family further proved both high- and low-affinity SBRs played critical roles in the differentiation expressions of genes regulating tiller number and spike sizes. Our results have provided numerous resources of SPLs’ downstream networks and wheat improvements, and revealed CRE variations are critical for subgenome divergences in the allohexaploid wheat.