Cardiac amyloidosis (CA) is a significant contributor to heart failure with preserved ejection fraction and is appreciating expanding therapeutic options. Non-invasive tools aimed at accurate identification and surveillance of therapeutic response are of immediate and expanding need. While native and post-contrast T1 mapping quantify expansion of the extra-cellular compartment from amyloid protein deposition, 3D strain analysis of non-contrast cine images offers unique advantages relevant to high prevalence of renal insufficiency in this population and reduced dependency on field strength, pulse sequence, and vendor implementation. We aimed to evaluate global and segmental associations between 3D strain and T1 mapping in patients with cardiac amyloidosis. Twenty consecutive patients with confirmed CA were recruited and underwent a standardized cardiovascular magnetic resonance imaging protocol at 3 T including using multi-planar cine imaging and T1 mapping using a shortened modified look-locker inversion recovery sequence. T1 mapping was performed pre- and (when permitted by renal function) post-contrast and measured for segmental T1 values. Spatially-matched 3D strain-based measures were similarly calculated. Mean left ventricular ejection fraction was 61 ± 21% (range 30–73%). Mean global native T1 was 1308 ± 96 ms. Post-contrast T1 and partition coefficient were 558 ± 104 ms and 0.85 ± 0.31, respectively. Global myocardial strain values were 8.1 ± 2.9% in the longitudinal direction, − 9.2 ± 3.4% in the circumferential direction, and 41.7 ± 22.8% in the maximum principal direction. Segmental analyses confirmed relative worsening in T1 values and reductions in strain values in the basal myocardial segments with relative sparing of the apical segments. Significant associations between T1 and strain-based measures were observed globally and segmentally, with the strongest associations found both globally and segmentally in the circumferential and minimum principal directions of deformation. This study identifies strong associations between 3D myocardial strain and T1-mapping based markers of regional amyloid protein deposition. These findings support expanded investigation of myocardial strain as a surrogate marker of response to novel therapeutic strategies in patients with cardiac amyloidosis.