Provided are a waveguide with which strain and defect caused by a manufacturing process or the like or caused in a semiconductor in an initial stage or during operation are suppressed so that improvement and stabilization of characteristics are expected, and a method of manufacturing the waveguide. A waveguide includes a first conductor layer and a second conductor layer that are composed of a negative dielectric constant medium having a negative real part of dielectric constant with respect to an electromagnetic wave in a waveguide mode, and a core layer that is in contact with and placed between the first conductor layer and the second conductor layer, and includes a semiconductor portion. The core layer including the semiconductor portion has a particular depressed and projected structure extending in an in-plane direction.