With a total of nearly 8,000, the DF4 is the most numerous diesel locomotive in China. 108 of the original DF4 variant were built from 1969 which had an output of 3,300 hp and a top speed of either 100 or 120 km/h for use in freight or passenger service. Due to insufficient reliability of the engine, the locomotives of the first variant often became unavailable.

The next two variants DF4A and DF4B were fitted with an upgraded version of the engine that had the same output, but better reliability. More than 4,500 DF4B were built, making it the most numerous variant. A variant derived from the DF4B was the DF4E, a two-section locomotive with only one cab in each section. With the DF4C built from 1985, the output of the engine was increased to 3,600 hp. A special variant was the DF4CK with the wheel arrangement A1A-A1A and a top speed of 160 km/h for higher-speed passenger service.

The latest major variant is the DF4D introduced in 1999. The engine now had an output of 4,000 hp and the locomotives now included traction equipment from the DF6 prototypes that had been developed in the eighties with the help of General Electric. It was built with different gear ratios with a top speed of 100, 145 or 170 km/h, with the fastest variant featuring an advanced suspension for the traction motors. One batch of the freight variant was built with radially adjustable axles.

Two prototypes derived from the DF4D were designated DF4DJ. These had three-phase traction equipment built in China with the help of Siemens and proved that three-phase traction was feasible for diesel locomotives. Despite the availability of more modern diesel locomotives, the DF4D is still being manufactured and there are even reports of the DF4B still being in production. In 2001, North Korea ordered two new DF4D and later received multiple older, refurbished ones. Multiple types of locomotives exported to several countries were also based on the DF4.