This paper presents EMGSense, a low-effort self-supervised domain adaptation framework for sensing applications based on Electromyography (EMG). EMGSense addresses one of the fundamental challenges in EMG cross-user sensing—the significant performance degradation caused by time-varying biological heterogeneity—in a low-effort (data-efficient and label-free) manner. To alleviate the burden of data collection and avoid labor-intensive data annotation, we propose two EMG-specific data augmentation methods to simulate the EMG signals generated in various conditions and scope the exploration in label-free scenarios. We model combating biological heterogeneity-caused performance degradation as a multi-source domain adaptation problem that can learn from the diversity among source users to eliminate EMG heterogeneous biological features. To relearn the target-user-specific biological features from the unlabeled data, we integrate advanced self-supervised techniques into a carefully designed deep neural network (DNN) structure. The DNN structure can seamlessly perform two training stages that complement each other to adapt to a new user with satisfactory performance. Comprehensive evaluations on two sizable datasets collected from 13 participants indicate that EMGSense achieves an average accuracy of 91.9% and 81.2% in gesture recognition and activity recognition, respectively. EMGSense outperforms the state-of-the-art EMG-oriented domain adaptation approaches by 12.5%-17.4% and achieves a comparable performance with the one trained in a supervised learning manner.