Portal vein thrombosis (PVT) is most commonly associated with cirrhosis due to the reduced blood flow through the liver. However, its occurrence in non-cirrhotic individuals is rare and typically linked to hypercoagulable states. The postpartum period is a recognized hypercoagulable state, yet PVT in this context remains uncommon. We report a rare case of PVT in a 25-year-old female patient diagnosed with a heterozygous prothrombin G20210A mutation, presenting six weeks after a cesarean section with recurrent epigastric pain, fever, and elevated cholestatic liver enzymes. Multifactorial etiologies, including the hypercoagulable postpartum period, prolonged bed rest, and the presence of the prothrombin G20210A mutation, contributed to the development of venous thrombosis. This case underscores the synergistic effect of genetic predisposition and pregnancy-related changes on thrombotic risk. It also highlights the importance of maintaining a high index of suspicion for PVT in postpartum females presenting with epigastric pain and fever. Our patient was successfully managed with anticoagulation therapy, which resolved her symptoms and normalized her liver function tests. This case raises critical questions about the long-term management of thrombotic risk in similar patients.