Food-borne diseases cause approximately 9.4 million illnesses each year in the United States, while globally, these diseases cause approximately 600 million cases of illness and [approximately] 420,000 deaths. Food contact surfaces, such as food packaging materials, food processing equipment surfaces, utensils, etc., are often responsible for the contamination of food with a variety of pathogens, including bacteria. To prevent such pathogens from contaminating edible goods, antimicrobial coatings can be applied on food contact surfaces. However, the global legal framework surrounding coatings for food contact surfaces necessitates that, in order to reach their full potential and application at food processing facilities, these coatings must not only exhibit the ability to kill bacteria, but must also demonstrate mechanical resistance to withstand external stressors, particularly those due to typical equipment sanitization procedures. In the present work, we describe our approach to designing, synthesizing, and characterizing an antimicrobial coating for food contact surfaces, based on the existing legal framework governing these materials, having both antimicrobial activity and mechanical durability, both of which are necessary before antimicrobial materials will earn wide-spread acceptance and adoption by the food processing industry. We focus on photocatalytic antimicrobial coatings, specifically, titanium dioxide coatings, fabricated using the sol-gel method. We explore the relationships among porosity, pore architecture, photocatalytic activity, antimicrobial behavior, and mechanical durability (primarily hardness and elastic modulus) of titanium dioxide coatings. During this exploration, we first optimized the photocatalytic activity of the coatings. Then, we optimized the mechanical durability of the coatings via a sequential response surface methodology to identify synthesis parameters that would lead to coatings with the highest photocatalytic activity and balanced values of hardness and elastic modulus. Once these conditions were identified and validated, the resulting optimized coatings were fully characterized and tested against food-borne bacteria Escherichia coli O157:H7. The results show that it is possible to achieve coatings with both sufficient antimicrobial activity and mechanical durability to withstand typical food processing operating conditions. In the long term, the long-term impact of this work can be enumerated as follows: (1) Development and validation of advanced and innovative technologies for food processing, manufacturing, packaging and sanitation that improve food safety and food defense, (2) Development of effective interventions for reducing contaminants in foods, and (3) Development and validation of novel strategies for the effective control of persistent reservoirs of food-borne pathogens.