This paper presents an agent-based modeling and simulation (ABMS) framework to evaluate the safety performance impacts of connected vehicle (CV) technologies in a work zone setting. This research is primarily motivated by the lack of a systematic evaluation platform to verify the safety benefits of CV technology in diverse settings, such as a work zone, caused by either a lane drop, speed reduction, or both. The guiding research question is how and when the safety benefits will start to appear as the market penetration (MP) level of CV increases and how the safety performance is affected with regard to free-flow, medium, and highly congested traffic conditions. Results show that the safety improvements are dependent on MP level and traffic flow rates. The higher the traffic flow rate, the higher MP level is needed to show improvement in the safety performance of the work zone section. In addition, a potential path of Vision Zero is likely to be achieved by an MP level of 100%. These results will inform the federal and state agencies’ decision makers to strategize the implementation of CV technologies and quantify the delicate balance between costs and benefits.