The origins of the railway station is a small station on the line Ghent-Ostend in 1881. At that time the main railway station of Ghent was the South railway station built in 1837. At the occasion of the 1913 world exhibition in Ghent, a new Sint-Pieters railway station was built. It was designed by architect Louis Cloquet and finished in 1912 just before the World Exhibition.
The station is built in an eclectic style with a long corridor dividing the building in its length which provides access to diverse facilities. A tunnel (designed by ir. P. Grondy) starting from the entrace hall provides access to the 12 platforms. This gives the station its cross-form design. The original waiting rooms for second and third class now serve as a buffet and restaurant.
The station was classified in 1995. In 1996 the station was renovated, with the renovation of the interior of the western wing completed in 1998.