Objectives: This study aimed to investigate the correlation between apical sparing of longitudinal strain (LS), as measured by speckle-tracking echocardiography (STE), and the histological presence of myocardial fibrosis (MF), in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Twenty-seven HOCM patients who underwent elective Morrow procedures +/− aortic valve replacement (AVR) were included. All patients had standard echocardiography, with STE pre- and post-operatively. Intraoperative probes of the interventricular septum were sent for histological analysis. Correlation of different regional LS patterns with the histological findings of MF and with clinical outcome were analyzed. In addition, a logistic regression and ROC analysis were performed. Results: All patients underwent the Morrow procedure for HOCM, with 33.3% also undergoing AVR. A total of 74.1% showed evidence of MF in the histological analysis. Patients with MF had significantly lower GLS than patients without MF (−12.7 ± 2.7% vs. −23.0 ± 5.7%, p < 0.001). The LS in patients with MF was significantly lower at the basal regions of the LV segments and increased significantly towards the apex as compared to the patients without MF (mean basal-strain %: −10.6 ± 2.6 vs. −17.3 ± 4.6, p < 0.001; mean apical strain %: −21.8 ± 4.8 vs. −16.7 ± 5.6, p = 0.032). In the logistic regression, only the GLS remained as an independent predictor of MF with an Odds ratio of 1.07 (95%-CI: 1.05–1.09, p < 0.001). Conclusions: Our study highlights the significant correlation between GLS and MF in HOCM patients. These findings contribute to the growing understanding of MF in HOCM and may inform future approaches to patient management and risk stratification.