Evaluating the climate change mitigation potential of the forest sector requires a holistic approach based on forest carbon (C) sequestration, C storage in harvested wood products (HWP) and substitution on markets. High uncertainty is associated with substitution factors, that express avoided fossil greenhouse gas (GHG) emissions from the use of forest-based products in replacement of GHG-intensive materials and fossil fuels. Few studies have focused on the development of substitution factors in Canada, resulting in the use of unrepresentative generic data. Here, we provide a framework to reduce uncertainties related to substitution factors for primary wood products in a Canadian context. A life cycle assessment framework is used to quantify fossil GHG emissions for a baseline and a wood-intensive scenario. For solid product substitution, we focused on the construction sector and analyzed a range of innovative wood buildings with steel and reinforced concrete as alternative materials. We found non-weighted averages of 0.80 tC/tC for sawnwood and 0.81 tC/tC for panels. For energy substitution, we analyzed cases with different specifications on biomass product, facility type and alternative fossil fuel source in non-residential heat production and biofuel transportation sectors. We found a non-weighted average of 0.80 tC/tC for non-residential heat production and 0.51 tC/tC for biofuel transportation, that can be interpreted as 0.91 tC/tC for heavy fuel oil, 0.69 tC/tC for light fuel oil and 0.68 tC/tC for natural gas substitution. These results provide a benchmark for substitution factors in Canada, to help guide forest management strategies for climate change mitigation.