Recognition of marine reservoir effect (MRE) spatial and temporal variability must be accounted for in any radiocarbon-based paleoclimate, geomorphological, or archaeological reconstruction in a coastal setting. ΔR values from 37 shell-wood pairs across southern Southeast Alaska provide a robust local evaluation of the MRE, reporting a local Early Holocene weighted ΔR average of 265 ± 205, with a significantly higher ΔR average of 410 ± 60 for samples near limestone karst. Integration with our synthesis of extant MRE calibrations for the Northwest Coast of North America suggests that despite local variability, regional ΔR averages echo proxies for coastal upwelling: regional weighted averages were at their highest in the Bølling-Allerød interstade (575 ± 165) and their lowest in the Younger Dryas stade (−55 ± 110). Weighted ΔR averages across the Northwest Coast rose to a Holocene high during the Early Holocene warm period (245 ± 200) before settling into a stable Holocene average ΔR of 145 ± 165, which persisted until the late Holocene. Our quantification of local and regional shifts in the MRE shines a light on present methodological issues involved in MRE corrections in mixed-feeder, diet-based calibrations of archaeological and paleontological specimens.