Metropolitan Police officers are investigating after being called to assist firefighters in Stonebridge, near Wembley, shortly after 1.20am.
A 43-year-old woman and three children, a 15-year-old girl, an eight-year-old boy and a four-year-old boy, died at the scene, the force said. Their next of kin have been informed.
Police are waiting for an update on the conditions of two others who were taken to hospital.
A 41-year-old man was arrested at the scene in connection with the incident and remains in custody.
Eight fire engines and around 60 firefighters responded to the blaze, the London Fire Brigade (LFB) said.
Two terrace houses, each with three floors, were severely damaged in the fire, which was under control by around 3.25am, the fire service added.
LFB assistant commissioner Keeley Foster said: “Upon arrival, firefighters were met with a well-developed fire, involving two adjoining properties. Crews immediately set to work carrying out firefighting operations in order to bring the incident under control.
“Sadly, a woman and three children have died as a result of this fire.
“Crews wearing breathing apparatus were able to rescue the woman and one of the children from the second floor, but they were later declared deceased at the scene.
“A further two children were discovered to have died in the fire, as crews carried out a search of the properties involved.”
She added: “This is an extremely tragic incident, and the thoughts of everyone across the brigade are with those impacted by this incident.”
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Superintendent Steve Allen, from the Met’s local policing team in northwest London, said: “This is an extremely tragic incident and our thoughts are with everyone involved.
“Officers arrested a man at the scene and we continue to work alongside investigators from the London Fire Brigade to establish the cause of the fire.
“Emergency services will remain in Tillett Close throughout the day as these enquiries take place.”
