Frame Relay and Asynchronous Transfer Mode (ATM) are two famous technologies in wide-area networks that use the virtual circuits for connecting and multiplexing many branches and networks. Those technologies can be used to carry different types of information such as real-time information which needs high data rate, low delay and an efficient throughput of the network's data communication devices. This paper is a study based on simulation for comparative performance evaluation between the Frame Relay and ATM to understand the overview and the nature of these technologies focusing on real-time applications using the OPNET simulation tool for analyzing the performance of voice application. The evaluation parameters are traffic sent, traffic received, delay, Jitter and the end-to-end delay which have been used to compare the performance of the ATM and Frame Relay in high-speed networks. The simulation results demonstrate that the ATM has high traffic sent, high traffic received, and less delay compared to the Frame Relay. In addition, this paper may be considered as an insight for the new researchers to guide them to an overview, essentials, and understanding of the virtual connections for Frame Relay and ATM.