Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy marked by late diagnosis, rapid progression, and poor prognosis, with a 5-year survival rate of 2–9%. Traditional tissue biopsy faces limitations in accessibility and real-time monitoring. Liquid biopsy—a minimally invasive technique analyzing tumor-derived materials such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, tumor-educated platelets (TEPs), and cell-free RNAs (cfRNAs)—offers dynamic insights into PDAC biology. This review advances beyond the prior literature by offering a unified synthesis that bridges molecular mechanisms, biomarker dynamics, and clinical translation within the context of PDAC. It also summarizes key clinical trials evaluating liquid biopsy in PDAC, underscoring its growing impact on precision oncology.