Originally laid down to connect the island city of Tenochtitlan with the southern shores of Lake Texcoco, in its present-day form it connects the city's downtown with the highways heading south out from the city to the states of Morelos and Guerrero over a distance of 18 km.

[3] Since 1970, line 2 of the Mexico City Metro runs down the Calzada de Tlalpan's median after emerging from its underground section at San Antonio Abad station.

The Xochimilco light rail continues down the Calzada after the metro's terminus at Tasqueña.

[1] Both transit systems follow the right-of-way of a former tram line.

[3] For vehicular traffic, the Calzada ends at its junction with Avenida Insurgentes in the borough of Tlalpan, where Federal Highways 95 and 95D continue south to Cuernavaca, Morelos, and beyond.