The development of advanced functional materials, capable of providing effective antimicrobial activity, has a big demand from the contemporary society. Advanced functional antimicrobial amorphous silica composites (ASC) are prepared by using sol–gel process and modified by Zn ions and rare-earth element Lu. The preparation conditions are optimized by single-factor analysis, and as-prepared functional hybrids are characterized by scanning electron microscopy (SEM), X-ray diffraction analysis, X-ray photoelectron spectroscopy (XPS), atomic adsorption spectrometry and inductively coupled plasma analyses. The presence of homogeneously mixed Zn and Lu, in the form of ZnO and Lu2O3, and dense micropores is confirmed by SEM and XPS. The amorphous structure and large surface area are beneficial for better antimicrobial performance. The as-prepared Zn–Lu ASC exhibited excellent antimicrobial properties against Escherichia coli and Staphylococcus aureus. We demonstrate that the addition of rare-earth element, Lu, has rendered synergistic effect on antimicrobial properties by increasing the release of Zn ions and generating excess reactive oxygen species. The present study provides a mechanistic insight and novel approach to fabricate functional antimicrobial materials for a wide range of applications.