Unmanned Aerial Vehicles (UAVs) are in the midst of aviation’s next generation. UAVs are being utilized at an increasing rate by military and security operations and are becoming widely popular in usage for activities such as search and rescue and weather research to homeland security and border patrol. In order for a safer integration of UAV’s within the National Airspace System (NAS), many research questions need to be addressed. This study examined the effects of system reliability and time pressure on UAV operator performance and mental workload. Twenty-four undergraduate and graduate students, male and female, from Embry-Riddle Aeronautical University participated in this study. An autonomous UAV simulator was used to engage the participants with a set if prescribed tasks. The primary task measures were image processing time and target acquisition accuracy. Three secondary tasks were concerned with responding to events encountered in typical UAV operations. Using the NASA-Task Load Index (TLX) form, mental workload for UAV autonomous systems was also analyzed. Results showed that system reliability has a significant effect on image processing time, while time pressure produced a significant effect for target acquisition accuracy. A significant effect was also found for the interaction between system reliability and time pressure for pop-up threats that required re-routing processing time. The results were examined and recommendations for future research are discussed