Thoracoabdominal aortic aneurysms (TAAAs) are rare and often remain asymptomatic until rupture, leading to high morbidity and mortality. Elastin degradation, largely mediated by matrix metalloproteinases (MMPs), plays a central role in their pathogenesis. This study aimed to evaluate plasma desmosine (pDES), a specific biomarker of elastin breakdown, as a non-invasive tool for TAAA detection and risk stratification. In a prospective single-centre case-control study, 30 patients with TAAA and 30 age- and sex-matched controls were enrolled. Plasma pDES levels were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Aortic wall samples from 12 patients were analysed for elastic fibre content and MMP expression by histology and western blotting. Statistical analyses included correlation testing, propensity score matching, and receiver operating characteristic (ROC) analysis. TAAA patients exhibited significantly higher pDES levels compared with controls (0.40 ± 0.31 vs. 0.22 ± 0.15 ng/mL; p < 0.001). pDES correlated positively with MMP-2 (ρ = 0.68, p = 0.02), TIMP-1 (ρ = 0.72, p = 0.01), and the proportion of elastic fibres in the aortic media (ρ = 0.61, p = 0.03). ROC analysis showed good diagnostic performance (AUC = 0.82), with a threshold of 0.27 ng/mL yielding 78.6% sensitivity and 76.7% specificity. Elevated pDES levels reflect aortic elastolytic activity and may serve as a promising biomarker for TAAA detection and risk assessment.