Based on the E3 class Atlantic, Alfred W. Gibbs developed the E6, which had a significantly larger boiler with similar overall dimensions. The heating surface of this boiler was about 36 percent larger than the E3, making the E6 the largest and most powerful Atlantic locomotive until the advent of the Milwaukee Road Class A streamlined locomotive in 1935. The PRR standard Belpaire firebox was used, which also had a combustion chamber. Only one prototype was built in 1911 for extensive testing, which was still operated with saturated steam. 

With the E6, the intention was to cover the fastest, but not exactly the heaviest express trains, for which a Pacific was not really needed. This means that a travel time of 18 hours could be planned for the route between New York City and Chicago. Compared to the K2 class Pacifics, the E6 delivered about the same power even at 40 mph and was even able to surpass it at higher speeds. The 235 miles from Altoona to Philadelphia could be covered in a test drive with an average of 67.4 mph. 

The only E6 was fitted with a superheater in 1914, increasing output by 30 percent and reducing water and coal consumption by 23 to 46 percent, depending on the situation. Between February and August 1914, 80 examples of the superheated variant were produced as E6s. They received different tenders with a water capacity between 7,100 and 7,400 gallons and a coal capacity between 26,900 and 34,350 pounds. The service life of the individual locomotives ended in the late 1940s and early 1950s.

The number 460, now known as “The Lindbergh Engine” and located in the Railroad Museum of Pennsylvania, gained particular notoriety. After Lindbergh's arrival back in Washington, several press agencies vied to get the photos of Lindbergh with President Coolidge to New York City as quickly as possible. While the competitors relied on airplanes for this, the International News Reel Corporation chose the train to be able to develop the photos on the go. The number 460 completed the 224.6 mile route with two passenger cars at an average speed of 72 mph. At one point it reached 115 mph, finishing an hour ahead of its competitors with the finished photos.