Lung ultrasound (LUS) is an effective tool for diagnosing acute heart failure (AHF). However, several imaging protocols currently exist and how to best use LUS remains undefined. We aimed at developing a lung ultrasound-based model for AHF diagnosis using machine learning. Random forest and decision trees were generated using the LUS data (via an 8-zone scanning protocol) in patients with acute dyspnea admitted to the Emergency Department (PLUME study, N = 117) and subsequently validated in an external dataset (80 controls from the REMI study, 50 cases from the Nancy AHF cohort). Using the random forest model, total B-line sum (i.e., in both hemithoraces) was the most significant variable for identifying AHF, followed by the difference in B-line sum between the superior and inferior lung areas. The decision tree algorithm had a good diagnostic accuracy [area under the curve (AUC) = 0.865] and identified three risk groups (i.e., low 24%, high 70%, and very high-risk 96%) for AHF. The very high-risk group was defined by the presence of 14 or more B-lines in both hemithoraces while the high-risk group was described as having either B-lines mostly localized in superior points or in the right hemithorax. Accuracy in the validation cohort was excellent (AUC = 0.906). Importantly, adding the algorithm on top of a validated clinical score and classical definition of positive LUS scanning for AHF resulted in a significant improvement in diagnostic accuracy (continuous net reclassification improvement = 1.21, P < 0.001). Our simple lung ultrasound-based machine learning algorithm features an excellent performance and may constitute a validated strategy to diagnose AHF.