Recent observations suggest that permafrost thaw may create two completely different soil environments: aerobic in relatively well-drained uplands and anaerobic in poorly drained wetlands. The soil oxygen availability will dictate the rate of permafrost carbon release as carbon dioxide (CO2) and as methane (CH4), and the overall effects of these emitted greenhouse gases on climate. The objective of this study was to quantify CO2 and CH4 release over a 500-day period from permafrost soil under aerobic and anaerobic conditions in the laboratory and to compare the potential effects of these emissions on future climate by estimating their relative climate forcing. We used permafrost soils collected from Alaska and Siberia with varying organic matter characteristics and simultaneously incubated them under aerobic and anaerobic conditions to determine rates of CO2 and CH4 production. Over 500 days of soil incubation at 15 °C, we observed that carbon released under aerobic conditions was 3.9–10.0 times greater than anaerobic conditions. When scaled by greenhouse warming potential to account for differences between CO2 and CH4, relative climate forcing ranged between 1.5 and 7.1. Carbon release in organic soils was nearly 20 times greater than mineral soils on a per gram soil basis, but when compared on a per gram carbon basis, deep permafrost mineral soils showed carbon release rates similar to organic soils for some soil types. This suggests that permafrost carbon may be very labile, but that there are significant differences across soil types depending on the processes that controlled initial permafrost carbon accumulation within a particular landscape. Overall, our study showed that, independent of soil type, permafrost carbon in a relatively aerobic upland ecosystems may have a greater effect on climate when compared with a similar amount of permafrost carbon thawing in an anaerobic environment, despite the release of CH4 that occurs in anaerobic conditions.