Mercury (Hg) is a global pollutant that has wide-ranging impacts on the physiological systems of birds, but almost nothing is known about how this affects migration. We manipulated methylmercury (MeHg) burdens of 24 wild-caught Yellow-rumped Warblers (Setophaga coronata) before releasing them and tracking their spring migration with automated radiotelemetry to study the effect of MeHg on stopover departure behavior and flight orientation. Dosing half the birds for 14 days prior to release resulted in environmentally relevant mean blood total Hg (THg) concentrations of 6.61 (± 0.16) p.p.m., while a group of 12 controls had nearly undetectable blood THg. We observed starkly different departure behavior between groups, with dosed birds leaving the release site significantly sooner than controls. Among birds that were detected beyond the release site, seven (three dosed, four control) initially made a landscape-scale relocation before a longer-distance migratory flight, while two (controls) migrated directly from the release site. All flights were in the seasonally appropriate direction regardless of group. Rapid departures by dosed birds could have been the result of hyperactivity that can be induced by MeHg, or due to decreased social dominance that caused them to seek areas with less resource competition. We found no evidence that MeHg impaired orientation, although sample sizes were small and we had less ability to detect birds flying in “incorrect” than northward directions. The dramatic difference in departure decisions between groups indicates a potential effect of MeHg on the neurological and/or physiological mechanisms that control migratory behaviors of birds.