After the Italian State Railways had found out that their three-phase network didn't have a future since it was too complex, they chose direct current for future use. For their new 3,000 Volt DC electrification program, they decided to introduce a mass-produced standard locomotive from early on. The requirements included that it had to be a mixed traffic locomotive suitable for freight, passenger and express trains. It also had to be rugged and easy to maintain.

In 1927, trials commenced with six E.625 and eight E.626 prototypes which were identical in most respects. While the E.625 had a gear ratio suitable for freight service and a top speed of 50 km/h, the E.626 was designed for passenger and express service with a top speed of 95 km/h. To get a real mixed traffic locomotive without different subclasses, it was soon decided to rebuild even the E.625 into E.626, since the tractive force was still high enough with the faster gear ratio.

Each locomotive had three two-axle bogies, of which the middle one was fixed in the frame. A wheel flange lubricator on the outermost axles ensured the best running characteristics in curves. The electric equipment was delivered by Tecnomasio Italiano Brown Boveri (TIBB).

With 448 locomotives built between 1927 and 1939, they set new production records and became the most numerous electric locomotive in the world. Over the years, their continuous power rose from 1,350 to 1,850 kW. Starting with number 100, they got electric train heating.

In Italy, the E.626 quickly spread over all DC electrified lines in the whole country. After World War II, 17 came to Yugoslavia and were used as class 361. Four came to Czechoslovakia, but only three were used. They were converted to the 1,500 V system used by then. In Italy, their active service only ended in 1999. Today, 14 are still existing.