Firefighters were called to Bedfont Road just after midnight.
The H26 bus was heading towards Hatton Cross before colliding head on with a silver Mercedes on a railway bridge.
Three people were declared dead at the scene, six others were taken to hospital and the bus was on fire when emergency crews arrived.
Assistant Commissioner Paul McCourt said: “The thoughts of everyone within the Brigade are with the families impacted by this tragic incident.
“I’d like to thank our crews and emergency service colleagues for the determination and dedication they showed when responding to this difficult situation.
“The Brigade will speak with our firefighters that attended and offer support through our counselling and trauma services where required.”