(1) Background: Acute pericarditis is often confused with ST-segment elevation myocardial infarction (STEMI) among patients presenting with acute chest pain in the emergency department (ED). Since a deep learning model (DLM) has been validated to accurately identify STEMI cases via 12-lead electrocardiogram (ECG), this study aimed to develop another DLM for the detection of acute pericarditis in the ED. (2) Methods: This study included 128 ECGs from patients with acute pericarditis and 66,633 ECGs from patients visiting the ED between 1 January 2010 and 31 December 2020. The ECGs were randomly allocated based on patients to the training, tuning, and validation sets, at a 3:1:1 ratio. We used raw ECG signals to train a pericarditis-DLM and used traditional ECG features to train a machine learning model. A human–machine competition was conducted using a subset of the validation set, and the performance of the Philips automatic algorithm was also compared. STEMI cases in the validation set were extracted to analyze the DLM ability of differential diagnosis between acute pericarditis and STEMI using ECG. We also followed the hospitalization events in non-pericarditis cases to explore the meaning of false-positive predictions. (3) Results: The pericarditis-DLM exceeded the performance of all participating human experts and algorithms based on traditional ECG features in the human–machine competition. In the validation set, the pericarditisDLM could detect acute pericarditis with an area under the receiver operating characteristic curve (AUC) of 0.954, a sensitivity of 78.9%, and a specificity of 97.7%. However, our pericarditis-DLM also misinterpreted 10.2% of STEMI ECGs as pericarditis cases. Therefore, we generated an integrating strategy combining pericarditis-DLM and a previously developed STEMI-DLM, which provided a sensitivity of 73.7% and specificity of 99.4%, to identify acute pericarditis in patients with chest pains. Compared to the true-negative cases, patients with false-positive results using this strategy were associated with higher risk of hospitalization within 3 days due to cardiac disorders (hazard ratio (HR): 8.09; 95% confidence interval (CI): 3.99 to 16.39). (4) Conclusions: The AI-enhanced algorithm may be a powerful tool to assist clinicians in the early detection of acute pericarditis and differentiate it from STEMI using 12-lead ECGs.