Background: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. Methods: The study population included patients with ESUS and non-cardioembolic (NCE) stroke presenting to statewide stroke center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the 3 phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow-up detection of AF in ESUS patients. Results: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266-2.986, p = 0.002), contractile (aOR 1.568, 95% CI 1.035-2.374, p = 0.034), and conduit strain (aOR 2.288, 95% CI 1.448-3.613, p = 0.001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029-6.236, p = 0.043), contractile strain (OR 2.828, 95% CI 1.158-6.903, p = 0.022), and conduit strain (OR 2.614, 95% CI 1.003-6.815, p = 0.049) were significantly associated with subsequent detection of AF. Conclusion: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies.