The Skyline name originated with the Prince automobile company which developed and sold the Skyline line of sedans before merging with Nissan-Datsun. The GT-R abbreviation stands for Gran Turismo Racer while the GT-B stands for Gran Turismo Berlinetta. The Japanese chose to use English when naming the car — as most cars made in Japan at that time used American abbreviation — to further enhance sales. The earliest predecessor of the GT-R, the S54 2000 GT-B, came second in its first race in 1964 to the purpose-built Porsche 904 GTS. The next development of the GT-R, the four-door PGC10 2000 GT-R, scored 33 victories in the one and a half years it raced, and by the time it attempted its 50th consecutive win, its run was ended by a Mazda Savanna RX-3. The car took 1000 victories by the time it was discontinued in 1972. The last of the original GT-Rs, the KPGC110 2000GT-R, used an unchanged S20 160 hp (120 kW) inline-6 engine from the earlier 2000 GT-R and only sold 197 units due to the worldwide energy crisis. This model was the only GT-R to never participate in a major race despite the sole purpose-built racecar which now resides in Nissan's storage unit for historical cars in Zama.

The Skyline continued into the 1990s when it became popular largely because it remained rear wheel drive, while most other manufacturers were focusing on front wheel drive cars.

After a 16 year hiatus after the KPGC110 Skyline GT-R of 1973, the GT-R version of the Skyline was reintroduced with the eighth generation Skyline R32 in 1989. The GT-R became the flagship of Nissan performance, showcasing many advanced technologies including the ATTESA-ETS 4WD system and the Super-HICAS four-wheel steering. The GT-Rs remained inexpensive compared to its European rivals, with a list-price of ¥ 4.5 million (about US$ 31,000).

GT-R Skylines of the 1990s progressed from the R32 (1989) through to the R34 (1999). Production of the GT-R ceased in August 2002. Although Nissan continues the Skyline name, a new GT-R was not developed as part of the lineup. However, Nissan later announced that they are producing a new GT-R as a separate car line, separating it from the Skyline nameplate. The new GT-R debuted in 2007.