Food safety science is an important field due to its practical applications in maintaining public safety and confidence in consumer goods. A significant component of food safety science is the detection and regulation of heavy metals in food. Heavy metals such as mercury (Hg) are of particular concern because of their potential to damage the nervous system, gastrointestinal tract, and other organ systems in humans and other organisms. The stringent standards and practices for the analysis of Hg in fish, as implemented by institutions such as the U.S. Food and Drug Administration (FDA), require both skilled analytical chemists and sensitive quantitative techniques, e.g., inductively coupled plasma mass spectrometry (ICP-MS). These needs inspired the development of an upper-division undergraduate analytical chemistry experiment that is designed to teach students how to quantify mercury in commercial fish products via ICP-MS analysis. In this hands-on laboratory exercise, students were taught how to use a standard reference material (SRM) for method validation and to understand how different matrices can affect the accuracy of the analysis. Students also learned how to optimize ICP-MS instrument parameters such as the kinetic energy discrimination (KED) voltage. Students worked in small groups and across lab sections to analyze their data and to identify the best parameter set for their experimental conditions. This lab exercise provides a rigorous, practical, and challenging experience for aspiring analytical chemists and can be readily adapted to the needs and interests of any institution with access to an ICP-MS instrument.