Recent studies have shown that the pathology workforce is at risk of decreased workplace well-being, which may lead to decreased job satisfaction, increased attrition, burnout, depression, anxiety, and suicidality, but there has been relatively little research on well-being initiatives designed for pathologists, pathology trainees, and laboratory professionals. Some studies have suggested that well-being initiatives may decrease burnout and increase workplace satisfaction and engagement. Here we describe the creation of a Pathology Wellness Committee in a large residency program. Interventions included emotional, social, and physical well-being interventions as well as system-based improvements. Additional initiatives were introduced in response to the increased stress, isolation, and social distancing guidelines during the height of the COVID-19 pandemic. The program's impact was measured by an annual House Staff Council Resident Wellness Survey over 4 years. The annual surveys showed improvements in workplace and residency program satisfaction and emotional well-being following system-based improvements and well-being initiatives. Physical and social well-being showed slight but not statistically significant decreases over the 4-year period. Results from the annual Accreditation Council for Graduate Medical Education Survey were also evaluated. We found that dedicated well-being initiatives in conjunction with system-based interventions may help improve overall well-being in pathology residents.