The use of supplementary cementitious materials (SCMs) is becoming increasingly popular for the production of sustainable concrete. However, in practice, replacement levels rarely exceed 50% and are often much lower, around 15%, with an emphasis on optimizing mechanical performance rather than material sustainability. In this research, 20, 40, 60, 80 and 100% of Portland cement (by weight) are replaced by SCMs. Four SCMs (two slags and two fly ashes) that are locally available in the Pacific Northwest of the United States are evaluated. Efficiency factors are used to describe the effect of the SCM replacement. Design expressions are developed for the four SCMs that allow for the optimization of material sustainability by maximizing SCM content based on a target compressive strength. Good agreement is seen between experimental and measured values, indicating the validity of the approach.