The use of fungicides to limit the development of soybean mycoses in modern agrocenoses is a common measure. At the same time, the use of symbiotic and phosphate-mobilizing bacteria increases the productivity and quality of the crop. The combination of biological agents and fungicides can have different effects and requires additional research. This study aimed to investigate the rhizosphere microbiome, mycosis resistance and soybean productivity under combined seed treatment with bacterial inoculants and fungicides. Pre-sowing treatment of soybean seeds was carried out with fungicides Maxim Star 025 FS or Kinto Duo, 12 hours after the seeds were inoculated with the complex bioformulation Ecovital based on Bradyrhizobium japonicum and Bacillus megaterium. The effect of the integrated seed treatment on the rhizosphere microbiome (by high-throughput sequencing), the level of mycosis development and soybean productivity was determined. Under the complex use of biological and chemical preparations, the biodiversity of the rhizosphere microbiome improved, the relative abundance of fungicide-resistant phyla increased, and the number of sensitive taxa decreased. The low abundance of native rhizobia populations indicated the need for pre-sowing inoculation of soybean seeds. The combined use of fungicides and inoculation of seeds with Ecovital contributed to the improvement of the effectiveness of plant protection against ascochitosis and septoria, and to an increase in soybean yield.