Officers and South Central Ambulance Service were called to a property in Archford Croft, Emerson Valley, just before midnight following reports of a stabbing having taken place.
One of the victims, a 17-year-old boy, died at the scene.
Another victim, also a 17-year-old boy, was taken to hospital with serious injuries but sadly later died.
The next of kin of both victims have been informed and are being supported by officers.
No arrests have currently been made.
Two adult males have also been injured in the incident and have been taken to hospital with serious, but not life-threatening injuries.
Head of Crime Detective Chief Superintendent Ian Hunter said: “Thames Valley Police is in the early stages of a double murder investigation after two teenage boys have tragically died in this shocking incident.
“Our priorities at this time are to conduct a thorough investigation and to support those who have been affected. Officers are currently at the scene which has been cordoned off and members of the public are asked to avoid the area.
“I would like to speak to anyone who has any information which could help with our enquiries or anyone who witnessed any suspicious activity in the area of Archford Croft at around the time of the incident around midnight.
“Even if you think details may be insignificant, please come forward and speak to police.
“I would also ask that anyone who has any information about what has happened to contact police via the 24-hour 101 number, quoting URN 1761 19/10.