To address the challenges of insufficient accuracy in detecting tomato disease object detection caused by dense target distributions, large-scale variations, and poor feature information of small objects in complex backgrounds, this study proposes the tomato disease object detection method that integrates prior knowledge attention mechanism and multi-scale features (PKAMMF). Firstly, the visual features of tomato disease images are fused with prior knowledge through the prior knowledge attention mechanism to obtain enhanced visual features corresponding to tomato diseases. Secondly, a new feature fusion layer is constructed in the Neck section to reduce feature loss. Furthermore, a specialized prediction layer specifically designed to improve the model’s ability to detect small targets is incorporated. Finally, a new loss function known as A-SIOU (Adaptive Structured IoU) is employed to optimize the performance of the model in terms of bounding box regression. The experimental results on the self-built tomato disease dataset demonstrate the effectiveness of the proposed approach, and it achieves a mean average precision (mAP) of 91.96%, which is a 3.86% improvement compared to baseline methods. The results show significant improvements in the detection performance of multi-scale tomato disease objects.