The construction of the railway started in 1921, to connect the North of Argentina with Chile across the Andes, and to serve the borax mines of the area.

It refers to an ancient Andean mountain pass between Argentina and Chile, located just in north of Socompa and projected as line terminus.

In 1923, after a Chilean request whose rail line arrived close to Socompa, the original project was abandoned and the Argentine route diverted to the current one.

[8] In March 2022, the Government of Salta Province met with executives of Chilean company Ferronor with the purpose of bringing back a passenger service between Argentina and Chile.

After the viaduct La Polvorilla, highest point of the line (4,220 m), the railway runs on the borders of Jujuy Province at Olacapato and, between Tolar Grande and Caipe, it crosses in the middle a dry lake named Salar de Arizaro.

Descending the western slopes of the Andes and the Atacama Desert, the "Huayitquina" reaches the industrial complex and village of La Negra and, after 22 km, the Pacific Ocean in the port city of Antofagasta.