River piracy—the diversion of the headwaters of one stream into another one—can dramatically change the routing of water and sediment, with a profound effect on landscape evolution. Stream piracy has been investigated in glacial environments, but so far it has mainly been studied over Quaternary or longer timescales. Here we document how retreat of Kaskawulsh Glacier—one of Canada’s largest glaciers—abruptly and radically altered the regional drainage pattern in spring 2016. We use a combination of hydrological measurements and drone-generated digital elevation models to show that in late May 2016, meltwater from the glacier was re-routed from discharge in a northward direction into the Bering Sea, to southward into the Pacific Ocean. Based on satellite image analysis and a signal-to-noise ratio as a metric of glacier retreat, we conclude that this instance of river piracy was due to post-industrial climate change. Rapid regional drainage reorganizations of this type can have profound downstream impacts on ecosystems, sediment and carbon budgets, and downstream communities that rely on a stable and sustained discharge. We suggest that the planforms of Slims and Kaskawulsh rivers will adjust in response to altered flows, and the future Kaskawulsh watershed will extend into the now-abandoned headwaters of Slims River and eventually capture the Kluane Lake drainage. River piracy—the diversion of one stream’s headwaters into another—has occurred on long timescales. An analysis of streamflow and digital elevation models documents river re-routing in response to glacier retreat in Yukon, Canada in May 2016.