The concrete subway overpass partially collapsed, and images and videos from the scene showed parts of a train hanging in mid-air.
A rescue operation is underway, the government said.
A video captured by an onlooker shows the parts of the train falling on cars below the overpass on the road.
Reuters reported that Mexico City Mayor Claudia Sheinbaum said that 15 people were killed and that a car was trapped under the rubble. On Twitter, Ms Sheinbaum wrote: “Unfortunately, there are dead and injured people. I am on-site supporting the installation of the command centre.”
Several local TV channels are showing footage of chaos at the accident site with crews searching for survivors. Videos on Mexican TV and social media showed train cars hanging and sirens blaring in the neighbourhood. On Milenio TV, firefighters and emergency workers were seen helping the survivors.
The crash occurred at 10:25 p.m. on Monday night. La Jornada reported that the injured have been taken to several hospitals.
The identity of the dead has not yet been revealed by the police.
The police had initially said that 13 were dead. It later revised the toll to 15.
Mexico’s civil protection agency said on Twitter that the derailment occurred on Line 12 of the subway system at Olivos Station in southeast Mexico City.
Marcelo Ebrard, Secretary of Foreign Relations of Mexico tweeted: “What happened today in the Metro is a terrible tragedy. My solidarity with the victims and their families. Of course, causes must be investigated and responsibilities defined. I reiterate myself at the entire disposal of the authorities to contribute in whatever is necessary.”
Olga Sánchez Cordero, head of the ministry of the Interior said on social media that investigations into the train accident must be carried out. She tweeted: “Solidarity and fraternity with the families affected by the tragedy tonight in the Metro and our support for the government of Mexico City. Investigations must be carried out and those responsible be determined as soon as possible. I will be very attentive to whatever is required.”