Murder-suicide (M-S) is a complex phenomenon that can involve a multifaceted set of interrelated biological and social factors. M-S is also sexed and gendered in that the perpetrators are most often male and their underpinning motives and actions link to masculinities in an array of diverse ways. With the overarching goal to describe connections between men, masculinities, and M-S, 296 newspaper articles describing 45 North American M-S cases were analyzed. The inductively derived findings revealed three themes: (a) domestic desperation, (b) workplace justice, and (c) school retaliation. Cases in the domestic desperation theme were characterized by the murder of a family member(s) and were often underpinned by men’s self-perceptions of failing to provide economic security. Workplace justice cases emerged from men’s grievances around paid-work, job insecurity, and perceptions of being bullied and/or marginalized by coworkers or supervisors. The school retaliation cases were strongly linked to “pay back” against individuals and/or society for the hardships endured by M-S perpetrators. Prevailing across the three themes was men’s loss of control in their lives, hopelessness, and marginalized masculine identities. Also evident were men’s alignments to hegemonic masculinities in reasserting one’s masculine self by protesting the perceived marginalization invoked on them. Overall, the findings give pause to consider the need for men-centered M-S prevention strategies to quell the catastrophic impacts of this long-standing but understudied men’s health issue.