Municipal solid waste (MSW) has become a global environmental issue due to the rapid development of economy, industrialization, and urbanization. Re-utilization of municipal solid waste incineration (MSWI) fly ash is a sustainable solution to address the environmental pollution of MSW. Here, we rationally develop a strategy to fabricate ceramic bricks with MSWI fly ash serving as the primary additive. Water absorption, shrinkage, and bending strength of the fly ash–derived ceramics meet the Chinese criterion of second-class ceramic tiles (GB16889-2008). Leaching toxicity tests demonstrate that leaching concentrations of heavy metals from ceramics are much lower than their limits of GB16889-2008, indicating a low potential hazard to surroundings. The biotoxicity of the fly ash–derived ceramics is evaluated through bioassays involving bacteria (Escherichia coli and Staphylococcus aureus) and mammalian cells (MG63). The results show that the fly ash–derived ceramics have favorable biosecurity, indicating that MSWI fly ash can be potentially utilized as raw materials to produce eco-friendly ceramics. Besides, this work provides a novel methodology to investigate the biosafety of recycled materials through the joint use of microorganisms and cells.