The United States is the world leader in incarceration—one in four of the world’s prisoners is in an American prison or jail. The United States incarcerates nearly 500,000 more people than the top 36 incarcerating European countries combined. The staggering expansion of the American criminal justice system, known as mass incarceration, began in the 1980s and has resulted in a social justice crisis that substantially overincarcerates of some of the most vulnerable and marginalized groups. At the beginning of the 21st century, the United States faces the immense challenge of rethinking and transforming its criminal justice system in ways that will alleviate racial and economic disparities, dramatically reduce the overreliance on incarceration as the means to public safety, and promote public safety. We propose a proactive, transdisciplinary, cross-sector, and empirically driven smart decarceration approach to transform the criminal justice system. Social work is uniquely qualified to lead the U.S. decarceration effort given its history of reform efforts, ethical commitment to social justice, and emerging leadership in structural and behavioral interventions to complex social problems. Social work can bring together siloed sectors and academic disciplines to create a rational response to human needs as prisons and jails devolve. Social work can pioneer the identification and implementation processes of evidence-driven smart decarceration to both ensure approaches that develop a socially just state of public safety and also prevent repeating history’s mistakes of mass incarceration.