<p>Anaerobic co-digestion of food waste (FW) and sewage sludge (SS) has shown superior performance over anaerobic mono-digestion. However, the fate of antibiotic resistance genes (ARGs) under various co-digestion ratios has been rarely reported to date. Thus, this study investigates the effects of FW:SS ratios on the digester’s performance and the fate of ARGs at different FW:SS ratios. The results demonstrated that at a 50:50 FW:SS ratio, 738&#xa0;mL.g⁻¹ VS of biogas and 393&#xa0;mL.g⁻¹ VS of methane were produced in the system on day 18. Response surface methodology (RSM) was also used for optimization, showing 42.5% FW is the optimal FW content for maximum biogas and minimum H₂S production. The distribution of select ARGs (<i>qnrS</i>, <i>tetA</i>, <i>emrB</i>, <i>bla</i>_<i>TEM</i>, <i>ampR</i>) was tracked in the liquid and solid fraction of the digestate. Results illustrated a decrease (83–99% reduction) in the overall abundance of the ARGs in the solid fraction after AD. A similar trend was observed for the ARGs in the liquid fractions (65–99% reduction), except for <i>ermB</i> which became 1.74–10.6-fold higher in the final digestate. Also, at 50% FW, the abundance of <i>intl1</i> increased in the liquid and solid fraction of digestate, indicating increased potential of ARG dissemination via horizontal gene transfer.</p> Graphical Abstract <p></p>