Background: Our objective was to determine the relevance of changes in myocardial mechanics in diagnosing and predicting cancer therapeutics-related cardiac dysfunction (CTRCD) in a community-based population treated with anthracyclines. Methods: Quantitative measures of cardiac mechanics were derived from 493 echocardiograms in 165 participants enrolled in the PREDICT study (A Multicenter Study in Patients Undergoing AnthRacycline-Based Chemotherapy to Assess the Effectiveness of Using Biomarkers to Detect and Identify Cardiotoxicity and Describe Treatment). Echocardiograms were obtained primarily at baseline (prior to anthracyclines), 6 and 12 months. Predictors included changes in strain; strain rate; indices of contractile function derived from the end-systolic pressure-volume relationship (end-systolic elastance (Eessb) and the left ventricular (LV) volume at an end-systolic pressure of 100 mm Hg (V100)); total arterial load (effective arterial elastance (Ea)) and ventricular-arterial coupling (Ea/Eessb). Logistic regression models determined the diagnostic and prognostic associations of changes in these measures and CTRCD, defined as a LV ejection fraction decline ≥10 to <50%. Results: By 12 months, 31 participants developed CTRCD. Longitudinal and circumferential strain and strain rate, V100, Ea, and Ea/Eessb each demonstrated significant diagnostic associations, with a 1-7% increased odds of CTRCD (p<0.05). Changes in longitudinal strain rate (area under the curve (AUC) 0.719 (95% CI 0.595 to 0.843)), V100 (AUC 0.796 (95% CI 0.686 to 0.903)) and Ea (AUC 0.742 (95% CI 0.632 to 0.852)) from baseline to 6 months were individually predictive of CTRCD at 12 months. Conclusions: Changes in non-invasively derived measures of myocardial mechanics are diagnostic and predictive of cardiac dysfunction with anthracycline chemotherapy in community populations. Our findings support the non-invasive assessment of measures of myocardial mechanics more broadly in clinical practice and emphasise the role of serial assessments of these measures during and after cardiotoxic cancer therapy.