The aim of this systematic review and meta-analysis was to investigate the overall accuracy of deep learning models in detecting periapical (PA) radiolucent lesions in dental radiographs, when compared to expert clinicians. Electronic databases of Medline (via PubMed), Embase (via Ovid), Scopus, Google Scholar, and arXiv were searched. Quality of eligible studies was assessed by using Quality Assessment and Diagnostic Accuracy Tool-2. Quantitative analyses were conducted using hierarchical logistic regression for meta-analyses on diagnostic accuracy. Subgroup analyses on different image modalities (PA radiographs, panoramic radiographs, and cone beam computed tomographic images) and on different deep learning tasks (classification, segmentation, object detection) were conducted. Certainty of evidence was assessed by using Grading of Recommendations Assessment, Development, and Evaluation system. A total of 932 studies were screened. Eighteen studies were included in the systematic review, out of which 6 studies were selected for quantitative analyses. Six studies had low risk of bias. Twelve studies had risk of bias. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of included studies (all image modalities; all tasks) were 0.925 (95% confidence interval [CI], 0.862-0.960), 0.852 (95% CI, 0.810-0.885), 6.261 (95% CI, 4.717-8.311), 0.087 (95% CI, 0.045-0.168), and 71.692 (95% CI, 29.957-171.565), respectively. No publication bias was detected (Egger's test, P = .82). Grading of Recommendations Assessment, Development and Evaluationshowed a "high" certainty of evidence for the studies included in the meta-analyses. Compared to expert clinicians, deep learning showed highly accurate results in detecting PA radiolucent lesions in dental radiographs. Most studies had risk of bias. There was a lack of prospective studies.