Automatic radiology report generation is a task that combines artificial intelligence and medical information processing, and it fully relies on computer vision and natural language processing techniques. Nowadays, automatic radiology report generation is still a very challenging task because it requires semantically adequate alignment of data from two modalities: radiology images and text. Existing approaches tend to focus on coarse-grained alignment at the global level and do not take into account the disease characteristics of radiology images at fine-grained semantics, which results in the generated reports potentially omitting key disease diagnostic descriptions. In this work, we propose a new approach, disease-knowledge-enhanced fine-grained image–text alignment for automatic radiology report generation (DKA-RG). The method combines global and disease-level alignment, thus facilitating the extraction of fine-grained disease features by the model. Our approach also introduces a knowledge graph to inject medical domain expertise into the model. Our proposed DKA-RG consists of two training steps: the image–report alignment stage and the image-to-report generation stage. In the alignment stage, we use global contrastive learning to align images and texts from a high level and also augment disease contrastive learning with medical knowledge to enhance the disease detection capability. In the report generation stage, the report text generated from the images is more accurate in describing the disease information thanks to sufficient alignment. Through extensive quantitative and qualitative experiments on two widely used datasets, we validate the effectiveness of our DKA-RG on the task of radiology report generation. Our DKA-RG achieves superior performance on multiple types of metrics (natural language generation and clinical efficacy metrics) compared to existing methods, demonstrating that the method can improve the reliability and accuracy of automatic radiology report generation systems.