Despite its projected crucial role in stringent, future global climate policy, non-CO2greenhouse gas (NCGG) mitigation remains a large uncertain factor in climate research. A revision of the estimated mitigation potential has implications for the feasibility of global climate policy to reach the Paris Agreement climate goals. Here, we provide a systematic bottom-up estimate of the total uncertainty in NCGG mitigation, by developing ‘optimistic’, ‘default’ and ‘pessimistic’ long-term NCGG marginal abatement cost (MAC) curves, based on a comprehensive literature review of mitigation options. The global 1.5-degree climate target is found to be out of reach under pessimistic MAC assumptions, as is the 2-degree target under high emission assumptions. In a 2-degree scenario, MAC uncertainty translates into a large projected range in relative NCGG reduction (40–58%), carbon budget (±120 Gt CO2) and policy costs (±16%). Partly, the MAC uncertainty signifies a gap that could be bridged by human efforts, but largely it indicates uncertainty in technical limitations.