This research examined the use of truck-only lanes to separate truck freight traffic from general passenger traffic along the 32-mi interstate highway (IH) 20 corridor between Dallas and Fort Worth, TX, United States. The corridor was selected because of its high truck percentage, locations of complex weaving and interactions between trucks and automobiles, and grade change issues that affect truck performance and raise safety concerns. The simulation-based modeling approach leveraged both mesoscopic and microscopic modeling methods. Dynamic traffic assignment (DTA)-based multiresolution modeling examined the regional impact of adding truck-only lanes along the entire IH 20 study corridor, whereas microsimulation focused on a specific segment with distinct operational challenges to model the interaction between truck traffic and general passenger traffic. The DTA mesoscopic model for the region predicted that around 3,000 trucks daily might shift to the dedicated truck-only lanes in both directions giving a travel time saving of 12% in each direction compared with the base case (no build). Focusing on the microsimulation case study to add an inside truck-only climbing lane on a 5-mi segment on IH 20, the model predicted an average increase in speed of 11 mph for eastbound traffic during the morning peak-hour but limited travel time benefits during the morning and afternoon peak hours in either direction. Reasonable safety and operational benefits were observed based on the analysis.