After the Union Pacific issued a requirement for a three-unit locomotive with a total power of 15,000 hp to replace their gas turbines, the GE U50 was one of the three contenders. The others were the EMD DD35A and the ALCO Century 855. All three designs combined two diesel engines and had a total of eight axles. The U50 used two 2,500 hp 16-cylinder engines which were also used in the U25B. Each one had its own generator and powered four axles on one end of the locomotive.

The trucks had been taken from the first generation gas turbines and were combined of two groups of two axles each, combined into a span bolster. In 1963, three units each were delivered to the Union Pacific and the Southern Pacific. After the first trials, the UP ordered 20 more and the SP none. 20 of the UP locomotives were retired in 1973 and 1974, only the remaining three and the three from the SP were used until 1977.

Some years later, the U50C was developed as an answer to the requirement for a locomotive with similar power that was optimized for power at speed. Since the original trucks were not suited for this, GE used three-axle trucks from the third generation gas turbines. To save weight, GE used two twelve-cylinders of the same power and modified many other parts, for example they now used aluminium cables instead of copper. Although 40 U50C had been built, they were not successful and had many failures in the fields of electrics, trucks, engines and dynamic brakes. All were retired in 1976.