GM-EMD had previously produced 3,600 hp locomotives, the SD45 and later SD45-2, but these used huge, 20-cylinder engines with high fuel consumption, and demand for them dropped sharply after the 1970s fuel crises. The SD50 used the same V16 645 as the SD40-2, but uprated to 3,500 hp from . This proved to be a step too far; the 50 series models were plagued by engine problems which harmed both sales and the reputation of EMD.
The subsequent SD60 model replaced the overstressed 645 engine with a new engine series, the 710.
The SD50's long hood saw changes from previous EMD models. The overall frame length was increased, and the long hood was made substantially longer. The resistors for the dynamic brake grid were moved from their previous location above the prime mover to a new, cooler location in front of the engine compartment air intakes, where they were more effectively separated from the rest of the locomotives' systems.
Depending on customer options, the SD50 was available with a multitude of traction-motor gearing ratio and wheel size options, the most common of which being the 70:17 ratio with 40 inch wheels, this allowed for a top speed of . Other gearing options for the SD50 with 40 inch wheels include 69:18 for , 67:19 for and 66:20 for . 42 inch wheels were also available.
The SD50 could be equipped with fuel tanks sizes from up to , had a lube oil capacity of and a cooling water capacity of .
The designation also applies to five locomotives built by EMD Australian licensee Clyde Engineering for Hamersley Iron. These were also shorter than production SD50s, and were equipped with a special double cab roof for insulation against the hot Australian desert sun. When withdrawn from Hamersley Iron service, they were sold to National Railway Equipment Company and exported to the U.S. in February 1999 and used in national lease service. They were subsequently sold to the Utah Railway in June 2001, where they remain.