In this study, regression modeling and analysis of factor-interactive effect on anaerobic biodegradation process (ABP) of food residues mixed with fruit-waste is presented. An experimental anaerobic digester simulating mesophilic conditions of most urban solid waste dumpsites was developed. The goal was to carry out regression modeling on anaerobic biodegradation process for biogas generation. The main-and interactive-effects of initial-pH, ash-loading and leachate-level were investigated. Response surface methodology with miscellaneous 3-level factorial design was employed. A second-order polynomial regression equation was generated that predicted biogas generation rate (BGR). Results indicated that within the experimental range of factors applied there was a single factor significant effect of initial-pH and ash-loading on ABP while leachate-level single effect was observed to be insignificant (α < 0.05). The two factor interactive-effects of initial-pH/ash-loading and leachate-level/ash-loading were found to be significant while that of initial-pH/leachate-level interactions was not significant. Verification tests yielded maximum BGR values that were in good agreement with predicted values thereby validating the regression model.