The ability to predict the anti-interference communications performance of unmanned aerial vehicle (UAV) data links is critical for intelligent route planning of UAVs in real combat scenarios. Previous research in this area has encountered several limitations: Classifiers exhibit low training efficiency, their precision is notably reduced when dealing with imbalanced samples, and they cannot be applied to the condition where the UAV’s flight altitude and the antenna bearing vary. This paper proposes the sequential Latin hypercube sampling (SLHS)-support vector machine (SVM)-AdaBoost algorithm, which enhances the training efficiency of the base classifier and circumvents local optima during the search process through SLHS optimization. Additionally, it mitigates the bottleneck of sample imbalance by adjusting the sample weight distribution using the AdaBoost algorithm. Through comparison, the modeling efficiency, prediction accuracy on the test set, and macro-averaged values of Precision, Recall, and F1-score for SLHS-SVM-AdaBoost are improved by 22.7%, 5.7%, 36.0%, 25.0%, and 34.2%, respectively, compared with Grid-SVM. Additionally, these values are improved by 22.2%, 2.1%, 11.3%, 2.8%, and 7.4%, respectively, compared with particle swarm optimization (PSO)-SVM-AdaBoost. Combining Latin hypercube sampling with the SLHS-SVM-AdaBoost algorithm, the classification prediction model of anti-interference performance of UAV data links, which took factors like three-dimensional space position of UAV and antenna bearing into consideration, is established and used to assess the safety of the classical flying path and optimize the flying route. It was found that the risk of loss of communications could not be completely avoided by adjusting the flying altitude based on the classical path, and that intelligent path planning based on the classification prediction model of anti-interference performance can realize complete avoidance of being interfered while reducing the route length by at least 2.3%, thus benefiting both safety and operation efficiency.