We present on- and offshore structural data from the Nazca-Panama plate boundary zone in the Gulf of Chiriquí and surrounding onshore areas of southwest Panama. Major offshore structures interpreted on multichannel seismic profiles from the Gulf of Chiriquí include Cébaco basin complex, a series of northeast-striking, Plio-Pleistocene half-grabens, and Montuosa basin, an asymmetric Plio-Pleistocene sag basin associated with a major strike-slip fault. We interpret Cébaco basin complex as a pull-apart basin between two major, left-lateral strike-slip faults that accommodate oblique motion between the Nazca plate and the mainland of southwestern Panama. Interpretation of regional seismic stratigraphic data indicates that the Plio-Pleistocene extensional phase that produced the Cébaco basin complex extended the area by about 7%. We studied outcrop-scale, conjugate strike-slip fault systems exposed on landmasses surrounding the Gulf of Chiriquí in order to place kinematic and age constraints on large-scale faults mapped on seismic profiles. Fault systems deforming Eocene to Lower Miocene sedimentary rocks on Coiba Island and the Azuero and Soná Peninsulas suggest an approximately northwest-southeast orientation of maximum extensional strain in an area that encompasses the offshore Cébaco basin complex. We propose three possible models to explain the observed pattern of strike-slip deformation observed in the Gulf of Chiriquí: (1) Neogene oblique subduction of the Nazca plate beneath Panama produces left-lateral strike-slip faulting and related northwest-oriented extension within the forearc (Gulf of Chiriquí) (2) Plio-Pleistocene shallow subduction/collision between the Cocos ridge and Costa Rica produces southwestward motion or “escape” of a Gulf of Chiriquí block that is detached from the rest of Panama by left-lateral strike-slip faults, and (3) Neogene bending of the Panama island arc following collision with the South American continent is accommodated in part by strike-slip motion and underthrusting along the southwest margin of Panama. Observed deformation may be a composite effect of more than one of these tectonic mechanisms.