Abstract Objective: This study investigates the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission potential in North Dakota, South Dakota, Montana, Wyoming, and Idaho from March 2020 through January 2021. Methods: Time-varying reproduction numbers, R _t , of a 7-d-sliding-window and of non-overlapping-windows between policy changes were estimated using the instantaneous reproduction number method. Linear regression was performed to evaluate if per-capita cumulative case-count varied across counties with different population size or density. Results: The median 7-d-sliding-window R _t estimates across the studied region varied between 1 and 1.25 during September through November 2020. Between November 13 and 18, R _t was reduced by 14.71% (95% credible interval, CrI, [14.41%, 14.99%]) in North Dakota following a mask mandate; Idaho saw a 1.93% (95% CrI [1.87%, 1.99%]) reduction and Montana saw a 9.63% (95% CrI [9.26%, 9.98%]) reduction following the tightening of restrictions. High-population and high-density counties had higher per-capita cumulative case-count in North Dakota on June 30, August 31, October 31, and December 31, 2020. In Idaho, North Dakota, South Dakota, and Wyoming, there were positive correlations between population size and per-capita weekly incident case-count, adjusted for calendar time and social vulnerability index variables. Conclusions: R _t decreased after mask mandate during the region’s case-count spike suggested reduction in SARS-CoV-2 transmission.