Developing novel, engaging courses in food safety is necessary to train professionals in this discipline. Courses that are interactive and case-based encourage development of critical thinking skills necessary for identifying and preventing foodborne disease outbreaks. The purpose of this study was to assess the efficacy of a case study module-based course for upper division undergraduate and graduate students interested in food safety. Four independent case study modules were developed and implemented by 4 universities working in tandem over a semester course. All case studies incorporated molecular and epidemiological methods employed by professionals in food safety in outbreak investigations. Each case study was based on a (i) suspect foodborne pathogen, (ii) identification tools including biochemical test variations and pulsed field gel electrophoresis, multiplex PCR and/or whole genome sequencing, and (iii) suspect location and company type from farm to production site to restaurant. Pre- and postinstruction evaluations revealed significant increases in understanding of the concepts introduced through each module as demonstrated by overall mean normalized gain of 0.32 ± 0.35 (15% ± 19%; n = 60). Institution, role of instructor, prescore, and learning environment all played a significant role in the effects of overall learning. This study provides a successful model for a case study-based course in food safety. The guidelines and materials developed by our group are available for use by other institutions.