Respiratory diseases impose a tremendous global health burden on large patient populations. In this study, we aimed to develop DeepMRDTR, a deep learning-based medical image interpretation system for the diagnosis of major respiratory diseases based on the automated identification of a wide range of radiological abnormalities through computed tomography (CT) and chest X-ray (CXR) from real-world, large-scale datasets. DeepMRDTR comprises four networks (two CT-Nets and two CXR-Nets) that exploit contrastive learning to generate pre-training parameters that are fine-tuned on the retrospective dataset collected from a single institution. The performance of DeepMRDTR was evaluated for abnormality identification and disease diagnosis on data from two different institutions: one was an internal testing dataset from the same institution as the training data and the second was collected from an external institution to evaluate the model generalizability and robustness to an unrelated population dataset. In such a difficult multi-class diagnosis task, our system achieved the average area under the receiver operating characteristic curve (AUC) of 0.856 (95% confidence interval (CI):0.843–0.868) and 0.841 (95%CI:0.832–0.887) for abnormality identification, and 0.900 (95%CI:0.872–0.958) and 0.866 (95%CI:0.832–0.887) for major respiratory diseases’ diagnosis on CT and CXR datasets, respectively. Furthermore, to achieve a clinically actionable diagnosis, we deployed a preliminary version of DeepMRDTR into the clinical workflow, which was performed on par with senior experts in disease diagnosis, with an AUC of 0.890 and a Cohen’s k of 0.746–0.877 at a reasonable timescale; these findings demonstrate the potential to accelerate the medical workflow to facilitate early diagnosis as a triage tool for respiratory diseases which supports improved clinical diagnoses and decision-making.