Since the passing of the Trafficking Victims Protection Act of 2000, anti-trafficking efforts have grown in funding, political strength, and popular-culture appeal in the United States and globally. Particularly influential in shaping anti-trafficking policy in the United States are anti-prostitution advocates who are primarily concerned with rehabilitating sex workers and eradicating sexual commerce. Simultaneous to the development of prohibitionist anti-trafficking and anti-prostitution efforts in the US, movements for sex worker rights have also grown in strength and visibility, influencing a variety of cultural, academic, and public health arenas. While sex worker activists have widened the dialogue around sex workers’ rights, their perspectives have not until recently been acknowledged by US policy makers. In this article, we first trace the recent social histories of both the new prohibitionist and the sex worker rights movements in the United States. Next, we describe the unprecedented collaborative activist process by which a human rights agenda for US-based sex workers was introduced and approved at the United Nations Human Rights Council through the Universal Periodic Review (UPR) process. We follow with an analysis of how the UPR process highlights the ongoing importance of the global human rights community for bringing a diversity of marginalised voices—including those of sex workers—to the attention of US policy makers. We conclude with an assessment of the unique policy reform opportunities and challenges faced by sex worker and human rights activists as a result of this historic moment.