A versatile, computationally efficient two-dimensional (2D) speckle-tracking method based on high resolution ultrasound imaging is proposed to quantify regional myocardial dysfunction in mice. Ultrasound scans were performed on the hearts of normal and post myocardial infarction (MI) mice with a Vevo770 scanner (VisualSonics, Toronto, Canada) operating at 30 MHz frequency. Regional myocardial motion was tracked using a 2D minimum sum of absolute differences (MSAD) block-matching algorithm. Motion analyses calculated from ultrasound images were compared with gold-standard analyses performed using small animal magnetic resonance imaging (MRI). The radial and circumferential components of strain were compared between ultrasound and MRI short axis views and promising correlations were obtained (r = 0.90 and r = 0.85 for radial and circumferential strain, respectively). Therefore, ultrasound imaging, followed by 2D image tracking, provides an effective, low cost, mobile method to quantify murine cardiac function accurately and reliably.