The prompt and precise identification of hemodynamically significant coronary artery lesions remains an ongoing challenge. This study investigated the diagnostic value of non-invasive global left ventricular myocardial work indices by echocardiography in functional status of coronary artery disease (CAD) patients with myocardial ischemia using fractional flow reserve (FFR) as the gold standard. A total of 77 consecutive patients with clinically suspected CAD were prospectively enrolled. All participants sequentially underwent echocardiography, invasive coronary angiography (ICA) and FFR measurement. According to the results of ICA, patients were divided into myocardial ischemia group (FFR ≤ 0.8, n = 27) and non-myocardial ischemia group (FFR > 0.8, n = 50). Myocardial work indices including global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), global positive work (GPW), global negative work (GNW), global systolic constructive work (GSCW) and global systolic wasted work (GSWW) were obtained by using the non-invasive left ventricular pressure strain loop (PSL) technique. Compared with the non-myocardial ischemia group, GWI, GCW, GPW and GSCW were significantly decreased in the myocardial ischemia group at either the 18-segment level or the 12-segment level (P < 0.001). At the 18-segment level, GWI < 1783.6 mmHg%, GCW < 1945.4 mmHg%, GPW < 1788.7 mmHg% and GSCW < 1916.5 mmHg% were optimal cut-off value to detect myocardial ischemia with an FFR ≤ 0.8. Global left ventricular myocardial work indices by echocardiography exhibited a good diagnostic value in patients with CAD and may have a good clinical significance for the screening of suspected myocardial ischemia.