Iron-overload cardiomyopathy is the principal cause of mortality in thalassemia. Via feature-tracking cardiac magnetic resonance (FT-CMR), we investigated alterations in cardiac deformation with the progression in myocardial iron overload (MIO). We enrolled 154 patients with thalassemia (50.64% male, mean age = 32.19 ± 9.79 years) referred for MIO assessment and 28 controls (50% male, mean age = 31.07 ± 4.35 years). Functional, strain, and T2* values were assessed in 4 study groups: no MIO (T2* > 20), mild-to-moderate MIO (T2* = 10-20), severe MIO (T2* < 10), and healthy controls. The recorded strain values were compared between the groups. The study groups were statistically significantly different vis-à-vis left ventricular (LV) global longitudinal strain (GLS) (F [3, 178] = 20.30), LV global radial strain (GRS) (F [3, 178] = 11.61), right ventricular (RV) GLS (F [3, 178]) = 5.32), RV global circumferential strain (GCS) (F [3, 178] = 26.02), and RVGRS (F [3, 178] = 16.86) (Ps < 0.005). The post hoc test revealed that LVGLS, RVGCS, and RVGRS were different between patients with thalassemia but without MIO and the control group (Ps < 0.001). A significant difference in LVGLS and LVGRS was detected between the T2* > 20 and 10 ≤ T2* ≤ 20 groups (Ps < 0.05). The multivariate logistic regression analysis depicted LVGRS as the most robust predictor of MIO (T2* ≤ 20) (odds ratio = 0.920, 95% CI 0.886 to 0.955), which predicted MIO with a cutoff point of 31.16% or less (sensitivity = 62% and specificity = 80.77%). Biventricular FT-CMR values are impaired in patients with thalassemia even without MIO. With MIO progression, LV strain values are the first ones to be undermined. Notably, functional CMR indices are jeopardized late, only after severe iron deposition.