Background Heart failure (HF) involves dysfunction of the left ventricle (LV) as well as left atrium and right ventricle. We characterized mechanical phenotypes of HF using 3-chamber strain echocardiography and compared their clinical outcomes. Methods and Results We retrospectively analyzed 3574 patients (median age, 74 years; male 52.8%) with acute HF who underwent 3-chamber strain echocardiography. Patients were classified as with LV, left atrium, or right ventricle myopathy if their corresponding strain values (LV global longitudinal strain, left atrium reservoir strain, and right ventricle global longitudinal strain) were lower than median cutoffs, respectively. The mechanical phenotypes of individual patients were characterized according to the combined myopathy. The primary outcome was a composite end point of 5-year all-cause mortality and HF hospitalization. During follow-up (median, 25.8 months), the primary outcome occurred in 1877 (52.5%) patients. Three-chamber strain values were independent predictors for the primary outcome. An incremental trend was observed for the primary outcome, along with the increasing numbers of combined myopathy. Each mechanical phenotype exhibited an increased risk of the primary outcome, with the highest risk observed in patients with 3-chamber myopathy (hazard ratio, 1.67 [95% CI, 1.42-1.96]). The prognostic significance of the mechanical phenotypes was feasible across the conventional HF subtypes stratified by LV ejection fraction. In HF with preserved ejection fraction, the presence of left atrium and right ventricle myopathy significantly increased the primary outcome, regardless of combined left ventricle myopathy. Conclusions Assessment of 3-chamber strain in HF enables characterization of distinctive mechanical phenotypes, which provides an independent prognostic value that may support long-term risk stratification.