Differentiating cardiac amyloidosis (CA) from hypertrophic cardiomyopathy (HCM) remains a clinical challenge, particularly in those with preserved left ventricular ejection fraction (LVEF) and similar hypertrophy. This study aimed to use left ventricular global function index (LVGFI) and myocardial contraction fraction (MCF) to discriminate CA from HCM without using contrast agents on cardiovascular magnetic resonance imaging (CMR). In total, we included 68 CA patients, 90 HCM patients, and 35 healthy controls. We found that LVGFI had excellent diagnostic performance in differentiating CA from HCM (area under the curve (AUC) = 0.91, 95% CI [0.86-0.95]), even in the challenging conditions of similar hypertrophy (AUC = 0.92, 95% CI [0.87-0.97]) and preserved LVEF (AUC = 0.90, 95% CI [0.84-0.96]). LVGFI also had significant correlations with LGE extent, NT-proBNP and troponin T (all p < 0.001). Multiple logistic regression analysis revealed that LVGFI was an independent predictor of CA (odds ratio: 1.11, 95% CI: 1.01-1.23; p = 0.034). In conclusion, LVGFI is a novel and clinically useful parameters with excellent ability in determining myocardial function and differentiating cardiac amyloidosis from hypertrophic cardiomyopathy.