Purpose: Patients with chronic Chagas cardiomyopathy (CCC) have a high mortality due to heart failure (HF). The aim of this study was to investigate clinical and echocardiographic predictors of incident HF in patients with CCC. Methods: Single-center retrospective longitudinal observational study which included 176 adult patients (59.1% women; 53.9 ± 10 years old; mean left ventricular [LV] ejection fraction 62% ± 10%) at an early stage of CCC (electrocardiogram and/or wall motion changes but no HF). The primary outcome was incident HF. The association between studied parameters with incident HF was performed by competing-risk survival regression models using the Fine and Gray method. Results: After a mean follow-up of 8.8 ± 3.6 years, 42 patients progressed to HF (27.04 cases/1000 patient-years). A model 0 adjusted for clinical and 2D-Doppler echocardiographic parameters and for all-cause mortality revealed diabetes mellitus (HR 4.91, 95% CI 1.67–14.4, p = 0.004), LV ejection fraction (HR 0.96, 95% CI 0.93–0.99, p = 0.022), and E’ velocity (HR 0.79, 95% CI 0.67–0.95, p = 0.01) as independently associated with incident HF. The addition of strain-derived parameters to model 0 revealed that LV global circumferential strain (HR 0.83, 95% CI 0.78–0.89, p < 0.001) and left atrial booster contraction strain (HR 1.14, 95% CI 1.02–1.28, p = 0.022) were associated with incident HF. Conclusion: While most clinical parameters were not associated with incident HF in patients with CCC, echocardiographic parameters, including LV systolic and diastolic function and strain-derived parameters, were associated with incident HF in patients with CCC. This knowledge can be very useful for planning the care and follow-up of these patients.