The safety enhancement of small fixed-wing UAVs regarding obstacle detection is addressed using optimization techniques to find the best sensor orientations of different multi-sensor configurations. Four types of sensors for obstacle detection are modeled, namely an ultrasonic sensor, laser rangefinder, LIDAR, and RADAR, using specifications from commercially available models. The simulation environment developed includes collision avoidance with the Potential Fields method. An optimization study is conducted using a genetic algorithm that identifies the best sensor sets and respective orientations relative to the UAV longitudinal axis for the highest obstacle avoidance success rate. The UAV performance is found to be critical for the solutions found, and its speed is considered in the range of 5–15 m/s with a turning rate limited to 45°/s. Forty collision scenarios with both stationary and moving obstacles are randomly generated. Among the combinations of the sensors studied, 12 sensor sets are presented. The ultrasonic sensors prove to be inadequate due to their very limited range, while the laser rangefinders benefit from extended range but have a narrow field of view. In contrast, LIDAR and RADAR emerge as promising options with significant ranges and wide field of views. The best configurations involve a front-facing LIDAR complemented with two laser rangefinders oriented at ±10° or two RADARs oriented at ±28°.