Guatemala, the most populous country in Central America, is haunted by the legacy of violence, political instability, poverty, corruption, and persisting, relentless inequality. Narco-trafficking routes through Central America became firmly established after air- and sea-based routes were disrupted by U.S. and Mexican drug enforcement efforts in the 1990s. Guatemala and its Central American neighbors were highly vulnerable to incursion by the drug trade, ideally-located between production sources and major consumers, its people and governments weakened by long-standing armed conflict. Evidence shows the drug trade disproportionately impacts Guatemala in comparison to the rest of the region. Its neighbors share similarly well-located geography and the legacy of armed conflicts, but Guatemala lacks the institutional strength and ability to combat the cartels. This paper posits that U.S. prohibitionist policies are ineffective and harmful to Guatemala’s people, based on a supply-reduction model and a review of previous literature and anecdotal evidence. Narco-trafficking and the United States’ drug enforcement efforts, strategies and policies, intensify existing violence, poverty, inequality and corruption within Guatemala, ensnaring its people in a recurring cycle of violence which reinforces barriers to escaping poverty and crime.