Background: Hypertension is a leading risk factor for cardiovascular diseases, primarily due to its adverse effects on ventricular-arterial (VA) coupling and subsequent target organ damage (TOD). This study investigates the utility of carotid-femoral pulse wave velocity (PWV) and global longitudinal strain (GLS) as novel markers for VA coupling in hypertensive patients. Methods: In a single-center observational analytical case-control study, 200 participants, comprising 150 hypertensive patients and 50 non-hypertensive healthy controls, were enrolled. Comprehensive assessments, including echocardiography, pulse wave velocity, and myocardial performance estimation were conducted. Comparing the PWV/GLS ratio to the conventional Ea/Ees ratio, the novel index of VA coupling was evaluated. Results: Hypertensive patients showed significant alterations in VA coupling parameters compared to controls. The PWV was notably higher in patients (11.1 ± 1.2 vs. 7.7 ± 0.8, p < 0.001), as was the Ea/Ees ratio (0.6 ± 0.1 vs. 0.48 ± 0.12, p < 0.001). Significant variations were observed in the PWV/GLS ratio among the groups (-0.66 ± 0.09 vs. -0.39 ± 0.04, p < 0.001), indicating altered VA coupling. ROC analysis demonstrated the superior predictive value of PWV/GLS for TOD, with AUCs significantly higher than those of Ea/Ees across various markers of TOD (IMT, diastolic dysfunction, LV mass index, and GLS). Multivariate logistic regression adjusted for confounders confirmed PWV/GLS as a significant predictor of TOD (p < 0.001). Conclusion: The PWV/GLS ratio emerges as a novel and superior marker for assessing ventricular-arterial coupling and predicting target organ damage in hypertensive patients, compared to the traditional Ea/Ees ratio.