With the recent growing interest of antibiotic resistance genes (ARGs) and their co-selection with heavy metal resistance genes (HMRGs), their relationship to heavy metals needs further analysis. This study examined the response of heavy metal resistant microorganisms (HMRMs) and antibiotic resistant microorganisms (ARMs) and their resistance genes (HMRGs and ARGs) to Cu and Cr stresses using metagenome. Results showed that Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Deltaproteobacteria, and Nitrospirae are the dominant HMRMs and ARMs, with majority of HMRMs taxa presenting changes similar to ARMs under heavy metal stresses. Types of HMRGs and ARGs changed (increased or decreased) under Cu and Cr stresses, and a significant relationship was noted between HMRGs and ARGs and their related microbe (p < 0.05). Network analysis revealed synergistic relationships between majority of HMRGs and ARGs; however, negative correlations were also noted between them. Co-occurrence of HMRGs and ARGs was mainly observed in chromosomes, and plasmids were found to provide limited opportunities for heavy metals to promote antibiotic resistance through co-selection. These findings imply that the response of HMRMs and ARMs is induced by heavy metals, and that the changes in these microbial communities are the main factor driving the diversity and abundance of HMRGs and ARGs. Display omitted •Metagenomic analysis of Cu and Cr stresses on resistance gene and their related microbe.•Changes of HMRMs and ARMs are significantly induced by different heavy metals.•Significant relationship was noted between HMRGs and ARGs and their related microbial community.•Microbial communities are the main factor driving the diversity and abundance of HMRGs and ARGs.