A cassava-based cropping system study assessed the short-term response of soil chemical and biochemical properties and soil microbial communities to soybean intercropping. Two soybean varieties (‘Select Manchuria’ and ‘Tiwala 12’) were tested as intercrops. The treatments did not affect the soil’s chemical (pH, OM, N, P, K) and biochemical (basal respiration and dehydrogenase and urease enzyme activities) properties after one cropping period. Amplicon sequencing analysis found that intercropping promoted the abundance of bacterial orders Actinomycetales, Solibacterales, Sphingomonadales, and Rhodospirillales. These groups play active roles in organic matter decomposition and can potentially improve the soil quality in an area by enhancing the soil’s organic matter content. In terms of community analysis, principal coordinate analysis (PCoA) and redundancy analysis (RDA) showed separation between mono and intercropping systems, while ANOSIM and PEMANOVA did not detect any significance between varieties and cropping systems for both bacterial and fungal data. These results suggest that, in the short term, introduction of soybean in a cassava-based cropping system affects selected microbial groups, but the overall influence in the microbial community is not distinctly detected.