Bedding-parallel (BPV), strike (SV), and cross-fold (CFV) veins represent a sequence of polyphase fracturing during the development of a fault-bend fold in lower Paleozoic carbonate beds in the Appalachian Valley and Ridge province, Pennsylvania. Brecciation and layer-parallel shearing played important roles in the development of the earliest vein set (BPV) which propagated prior to folding. Fluid inclusions in calcite BPV are highly saline brines (23.4 wt% NaCI) trapped at conditions close to lithostatic (P ≤ 180 MPa, T ≤ 267 °C). While passing through the lower kink plane of a fault-bend fold, strike joints propagated in dolomitic beds located on the extensional side of neutral surfaces. Stylolitization of strike joint surfaces accompanied slip of the hanging wall up a ramp. Renewed extension upon passing through a second kink plane led to propagation of antitaxial SV along the stylolitized joints by the crack-seal process. Slightly less saline fluids (22.4 wt% NaCI) were trapped in SV at fluid pressures ≤144 MPa and temperatures ≤217 °C. With the concurrent formation of lateral ramps, the carbonates moved to the upper flat and were subjected to strike parallel extension as manifested by the propagation of antitaxial CFV. Due to further mixing of fresh waters, the salinity of fluids forming CFV decreased (20.5 wt% NaCl) with trapping conditions at P ≤ 116 MPa and T ≤ 179 °C. The fluid evolution path from BPV to CFV through SV shows a modest decrease in salinity with a sharp decrease in possible trapping pressures.