Epilepsy, a neurological disorder marked by recurrent, unprovoked seizures, is often linked to dysregulated iron metabolism, resulting in iron overload and subsequent cellular dysfunction or death within epileptogenic regions. We proposed a specific, noninvasive technique using paramagnetic susceptibility imaging via magnetic resonance imaging to quantify in vivo brain iron levels, aiming to enhance our understanding of epilepsy pathology and improve diagnostic accuracy. Our imaging and histopathological studies demonstrated that paramagnetic susceptibility is a sensitive biomarker for iron quantification in epilepsy. This method effectively detects iron abnormality from various causes and highlights that iron alters within epileptogenic zones, indicating the presence of potentially salvageable tissue. Furthermore, iron accumulation was observed to disrupt cortical laminar structures in epileptogenic zones and was associated with the proliferation of central nervous system cells, particularly astrocytes. Paramagnetic susceptibility imaging provides previously unknown insights into epilepsy, offering potential applications in diagnostics, monitoring, and personalized treatment strategies.