It travels 25.1 kilometers (15.6 mi) along the boroughs of Benito Juárez, Iztapalapa and Tláhuac in southwestern, central-southern and southeastern Mexico City, serving twenty stations.

All the stations are accessible to people with disabilities as they have elevators, tactile pavings and braille signage plates.

Line 12 was built by Mexican construction company Empresas ICA in association with Alstom Mexicana and Grupo Carso.

However, due to time and budget constraints the project underwent modifications after its announcement, and it became a combined under- and overground line with steel-tired trains running elevated along Tláhuac Avenue.

Subsidence was reported on several columns along the elevated section before testings with trains started.

In the 1980s, the Comisión de Vialidad y Transporte Urbano (COVITUR), an organization of the Federal District Department, presented a plan for the Mexico City Metro based on several studies and reports related to the rapid growth of the city and its demand for public transportation.

The document considered the new demand for public transport as well as the urban expansion towards the suburbs and the neighboring State of Mexico.

In July 2007, the city announced a query among its citizens, named Consulta Verde, to choose between two routes.

[7] The announced stations from west to east, with their original names, were: Mixcoac, Insurgentes Sur, 20 de Noviembre (later renamed to Hospital 20 de Noviembre), Zapata, Parque de los Venados, Eje Central (otherwise known as Popocatépetl), Ermita, Sur 69, Vía Láctea, Mexicaltzingo, Francisco del Paso, Ganaderos (otherwise known as Granaderos), Canal Nacional, ESIME Culhuacán, La Vírgen, Calle 11, Periférico Oriente, Tezonco (also known as San Lorenzo), Olivos (also known as Los Olivos), Francisco Villa (later renamed to Nopalera), Zapotitlán, Tlaltenco and Tláhuac.

For instance, Sur 69 and Vía Láctea stations were not built due to neighborhood opposition.

Ganaderos station was rejected by the National Institute of Anthropology and History because its construction would have affected a nearby archaeological site.

[15] Starting on 16 June 2012, the STC allowed riders to have access on Sundays to test the service and to familiarize them with the stations and route.

[16] The line began daily service on Monday 24 September 2012,[17] and it was officially inaugurated on 30 October 2012 by Marcelo Ebrard, Head of Government of the Federal District from 2006 to 2012 and Felipe Calderón, President of Mexico from 2006 to 2012.

[18][19] In an unprecedented event in the history of Mexico City Metro, Line 12 had to be shut down temporarily in the stretch Tláhuac–Atlalilco due to severe faults in its infrastructure.

[15] The stretch was closed between 12 March 2014 and 29 November 2015, when the section going from Tezonco to Tláhuac was officially reopened by Miguel Ángel Mancera, Head of Government of the Federal District from 2012 to 2018.

[33] Mixcoac station, the provisional western terminus of the line, lies along Extremadura Avenue (Eje 7 Sur), in the neighborhood of the same name.

It continues along the avenue to Culhuacán, San Andrés Tomatlán, Lomas Estrella, Calle 11, Periférico Oriente, Tezonco, Olivos, Nopalera and Zapotitlán stations.

It arrives at Tlaltenco station,[42] and later to the southeastern terminal of Tláhuac, along San Rafael Atlixco Avenue.

The project was approved in September 2013 by Gerardo Ruiz Esparza, Secretary of Communications and Transportation.

According to the data provided by the authorities, the line registered 134,900,367 entrances, averaging 369,590 commuters per day in 2019.