Modern cone-beam CT systems, especially C-arms, are capable of diverse source-detector orbits. However, geometric calibration of these systems using conventional configurations of spherical fiducials (BBs) may be challenged for novel source-detector orbits and system geometries. In part, this is because the BB configurations are designed with careful forethought regarding the intended orbit so that BB marker projections do not overlap in projection views. Examples include helical arrangements of BBs (Rougee et al 1993 Proc. SPIE 1897 161-9) such that markers do not overlap in projections acquired from a circular orbit and circular arrangements of BBs (Cho et al 2005 Med. Phys. 32 968-83). As a more general alternative, this work proposes a calibration method based on an array of line-shaped, radio-opaque wire segments. With this method, geometric parameter estimation is accomplished by relating the 3D line equations representing the wires to the 2D line equations of their projections. The use of line fiducials simplifies many challenges with fiducial recognition and extraction in an orbit-independent manner. For example, their projections can overlap only mildly, for any gantry pose, as long as the wires are mutually non-coplanar in 3D. The method was tested in application to circular and non-circular trajectories in simulation and in real orbits executed using a mobile C-arm prototype for cone-beam CT. Results indicated high calibration accuracy, as measured by forward and backprojection/triangulation error metrics. Triangulation errors on the order of microns and backprojected ray deviations uniformly less than 0.2 mm were observed in both real and simulated orbits. Mean forward projection errors less than 0.1 mm were observed in a comprehensive sweep of different C-arm gantry angulations. Finally, successful integration of the method into a CT imaging chain was demonstrated in head phantom scans.