TFC (10% thifluzamide–fludioxonil–clothianidin) is a novel wheat seed-coating agent. In the field, we confirmed that 10% TFC plays a positive role in preventing soil-borne diseases and promoting wheat seedling growth. However, its effects on rhizosphere microecology and the underlying molecular mechanism are not fully understood. Field trials revealed a positive effect on the biomass, plant height, and root length of wheat sharp eyespots in a Yingshang field, with 95.3% control efficiency. The effects of 10% TFC on the rhizosphere soil microbiome of young wheat plants were evaluated using high throughput sequencing technology. The results demonstrated that seed-coating agents significantly changed bacterial and fungal communities, and reduced the number of bacteria but increased the number of fungi. Sequence analysis revealed that the abundance of Proteobacteria, Actinobacteria, and Patescibacteria in bacteria and Ascomycota, Mortierellomycota, and Basidiomycota in fungi were significantly enriched, which have been reported as being beneficial for plant growth and pathogen resistance. In contrast, the abundance of Mucoromycota in fungi was reduced, and most of the related genera identified were pathogenic to plants. In this study, 15-day-old wheat plant tissues treated with 10% TFC were subjected to global transcriptome analysis by RNA sequencing to provide insights into the effects of 10% TFC on seedling growth. The comparative analysis of Triticum aestivum L. libraries identified 8286 differentially expressed genes (DEGs), of which 2290 and 5996 genes were up- and downregulated in seedling growth in the presence of 10% TFC, respectively. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses were performed for up- and downregulated DEGs separately, showing that these DEGs were enriched for terms related to the phenylpropanoid biosynthesis pathway, the protein products of which promote cell differentiation and seedling growth. This research provides comprehensive insights into its effects on wheat seedling growth and the rhizosphere microecology of seed coatings and provides important insights into their regulation and into understanding the potential benefits of seed coatings in disease management and plant growth promotion.