Current clinical ultrasound-based methods for plaque characterization are limited to visual assessment of plaque echogenicity creating demand for quantitative diagnostic tools. Our objective was to validate radial and longitudinal speckle tracking (ST) strain in phantom plaques via sonomicrometry (sono), and to compare the peak plaque and arterial wall strain. Four carotid artery gel-phantoms with a soft wall inclusion, mimicking a vulnerable plaque, were constructed. The phantoms were connected to a programmable pump simulating a carotid flow. Cineloops were acquired using a GE Vivid E9 where radial and longitudinal strain were calculated using a normalized cross-correlation ST algorithm. The region of interest was adjusted according to the plaque size. Sonomicrometry was used as a reference measurement. The correlation between estimated mean peak strain and the reference peak strain was r = 0.96 (p < 0.001) radially and r = 0.75 (p ≤ 0.005) longitudinally. The soft plaque exhibited 35.1% (SD 16.9%) greater radial (p < 0.001) and 88.6% (SD 72.0%) greater longitudinal (p < 0.001) peak strain than the arterial wall when measured with speckle tracking. It was possible to estimate plaque strain by ST and to distinguish a soft plaque from the vessel wall via strain measurements.