Background: The need for autonomous aerial surveillance originates from weaknesses in manual monitoring, such as late response, low scalability and rigid patrol plans. AI and GPS-driven smart aerial monitoring present an attractive solution for continuous adaptive wide-area surveillance. Objective: In this paper, we aim at designing and validating experimentally a low-cost drone-based unmanned autonomous mission patrolling system with waypoint navigation, real-time video backhauling, AI-based human/object detection and GPS path re-planning when an event occurs to ensure the safety of patrol missions under battery constraints. Methods: The proposed architecture combines autonomous navigation and embedded flight-control with online analog video streaming and ground-station-based computer vision processing. Object detection based on deep learning for live aerial video is used, and the proposed system’s performance is tested at different altitudes, lighting states and GPS patrol plans. Results: Experimental results show that the proposed method can obtain stable waypoint tracking with a clear real-time video downlink in patrol missions. The system is able to adaptively modify paths as a reaction to detected events and commence safe return-to-home functionality during low-battery conditions. The proposed detection model obtains a mean average precision of 87.4%, with an F1-score of 0.89 and real-time inference latency (20–25 ms per frame) that enables fast service without any interruption in practice during surveillance deployment. Conclusions: Experimental results show that the proposed method can obtain stable waypoint tracking with a clear real-time video downlink in patrol missions. The system can adaptively modify paths as a reaction to detected events and commence safe return-to-home functionality during low-battery conditions. The proposed detection model obtains a mean average precision of 87.4%, with an F1-score of 0.89 and real-time inference latency (20–25 ms per frame) that enables fast service without any interruption in practice during surveillance deployment.