Deep learning (DL) can fail when there are data mismatches between training and testing data distributions. Due to its operator-dependent nature, acquisition-related data mismatches, caused by different scanner settings, can occur in ultrasound imaging. As a result, it is crucial to mitigate the effects of these mismatches to enable wider clinical adoption of DL-powered ultrasound imaging and tissue characterization. To address this challenge, we propose an inexpensive and generalizable method that involves collecting a large training set at a single setting and a small calibration set at each scanner setting. Then, the calibration set will be used to calibrate data mismatches by using a signals and systems perspective. We tested the proposed solution to classify two phantoms using an L9–4 array connected to a SonixOne scanner. To investigate generalizability of the proposed solution, we calibrated three types of data mismatches: pulse frequency mismatch, focus mismatch, and output power mismatch. Two well-known convolutional neural networks (CNNs), i.e., ResNet-50 and DenseNet-201, were trained using the ultrasound radio frequency (RF) data. To calibrate the setting mismatches, we calculated thesetting transfer functions. The CNNs trained without calibration resulted in mean classification accuracies of around 52%, 84%, and 85% for pulse frequency, focus, and output power mismatches, respectively. By using thesetting transfer functions, which allowed a matching of the training and testing domains, we obtained the mean accuracies of 96%, 96%, and 98%, respectively. Therefore, the incorporation of thesetting transfer functionsbetween scanner settings can provide an economical means of generalizing a DL model for specific classification tasks where scanner settings are not fixed by the operator.