Lyme disease can lead to neurological, cardiac, and rheumatologic complications when untreated. Timely recognition of the erythema migrans rash of acute Lyme disease by patients and clinicians is crucial to early diagnosis and treatment. Our objective in this study was to develop deep learning approaches using deep convolutional neural networks for detecting acute Lyme disease from erythema migrans images of varying quality and acquisition conditions. This study used a cross-sectional dataset of images to train a model employing a deep convolutional neural network to perform classification of erythema migrans versus other skin conditions including tinea corporis and herpes zoster, and normal, non-pathogenic skin. Evaluation of the machine's ability to classify skin types was also performed on a validation set of images. Machine performance for detecting erythema migrans was further tested against a panel of non-medical humans. Online, publicly available images of both erythema migrans and non-Lyme confounding skin lesions were mined, and combined with erythema migrans images from an ongoing, longitudinal study of participants with acute Lyme disease enrolled in 2016 and 2017 who were recruited from primary and urgent care centers. The final dataset had 1834 images, including 1718 expert clinician-curated online images from unknown individuals with erythema migrans, tinea corporis, herpes zoster, and normal skin. It also included 116 images taken of 63 research participants from the Mid-Atlantic region. Two clinicians carefully annotated all lesion images. A convenience sample of 7 non-medically-trained humans were used as a panel to compare against machine performance. We calculated several performance metrics, including accuracy and Kappa (characterizing agreement with gold standard), as well as a receiver operating characteristic curve and associated area under the curve. For detecting erythema migrans, the machine had an accuracy (95% confidence interval error margin) of 86.53% (2.70), ROCAUC of 0.9510 (0.0171) and Kappa of 0.7143. Our results suggested substantial agreement between machine and clinician criterion standard. Comparison of machine with non-medical expert human performance indicated that the machine almost always exceeded acceptable specificity, and could operate with higher sensitivity. This could have benefits for prescreening prior to physician referral, earlier treatment, and reductions in morbidity.