The combination of multi-phase extension and pre-existing fault reactivation results in a complex fault pattern within hydrocarbon-bearing basins, affecting hydrocarbon exploration at different stages. We used high-resolution 3D seismic data and well data to reveal the impact of multi-phase extension and pre-existing fault reactivation on Cenozoic fault pattern changes over time in the Jiyang Depression of eastern China. The results show that during the Paleocene, a portion of NW-striking pre-existing faults reactivated under NS extension and controlled the basin structure (type 1). Other parts of the NW-striking pre-existing faults stopped activity and served as weak surfaces, and a series of NNE-striking faults were distributed in an en-echelon pattern along the NW direction at shallow depths (type 2). In areas unaffected by pre-existing faults, NE-striking faults formed perpendicular to regional stresses. During the Eocene, the regional stresses shifted clockwise to near-NS extension, and many EW-striking faults developed within the basin. The NE-striking faults and the EW-striking faults were hard-linked, forming the ENE-striking curved faults that controlled the structure in the basin (type 3). The NNE-striking faults were distinctly strike-slip at this time, with the ENE-striking faults forming a horsetail pattern at their tails. Many ENE-striking faults perpendicular to the extension direction were formed in areas where the basement was more stable and pre-existing faults were not developed (type 4). There were also developing NS-striking faults that were small in scale and appeared in positions overlapping different main faults (type 5). Additionally, different fault patterns can guide different phases of hydrocarbon exploration. Type 1, type 2, and type 3 faults are particularly suitable for early-stage exploration. In contrast, type 4 and type 5 faults are more appropriate for mature exploration areas, where they may reveal smaller hydrocarbon reservoirs.