Polyamide 6 (PA6) fiber has the advantages of high strength and good wear resistance. However, it is still challenging to effectively load inorganic antibacterial agents into polymer substrates without antimicrobial activity. In this work, graphene oxide is used as a carrier, which is modified with an aminosilane coupling agent (AEAPTMS) to enhance the compatibility and antimicrobial properties of the inorganic material, as well as to improve its thermal stability in a high‐temperature melting environment. Cuprous oxide‐loaded aminated grapheme (Cu2O‐GO‐NH2) is constructed by in situ growth method, and further PA6/Cu2O‐GO‐NH2 fibers are prepared by in situ polymerization. The composite fiber has excellent washing resistance. After 50 times of washing, its bactericidal rates against Bacillus subtilis and Escherichia coli are 98.85% and 99.99%, respectively. In addition, the enhanced compatibility of Cu2O‐GO‐NH2 with the PA6 matrix improves the orientation and crystallinity of the composite fibers. Compared with PA6/Cu2O‐GO fibers, the fracture strength of PA6/Cu2O‐GO‐NH2 fibers increases from 3.0 to 4.2 cN/dtex when the addition of Cu2O‐GO‐NH2 is 0.2 wt%. Chemical modification and in situ concepts help to improve the compatibility of inorganic antimicrobial agents with organic polymers, which can be applied to the development of medical textiles.