The incident happened in Old Kent Road in Bermondsey at around 10.45pm last night (August 27).
Officers and London Ambulance Service crews attended and found three boys who had been stabbed.
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One remains in hospital in a life-threatening condition.
The second was taken to hospital where his injuries were deemed not life-changing or threatening.
Following a pursuit a 17-year-old boy was arrested by officers on suspicion of attempted murder.
He remains in police custody.
A spokesperson for Metropolitan Police said: “If you have any information that could help police, please call 101 quoting CAD 8387/27AUG.
“If you wish to remain anonymous, please speak with Crimestoppers on 0800 555 111.
“Old Kent Road eastbound remains closed at this stage. Please avoid the area where possible.
“We understand the concern this incident will cause within the local community.
“Residents can expect to see an increased police presence in the area over the coming days.”
A spokesperson for London Ambulance Service said: “We were called at 10.44pm on Wednesday 27 August to reports of a stabbing on Old Kent Road, SE1.
“We sent resources to the scene, including ambulance crews, an advanced paramedic, a paramedic from our tactical response unit and an incident response officer.
“We also dispatched a trauma team from London’s Air Ambulance, which consists of a doctor and a paramedic in a car.
“We treated three patients for stab wounds and took them to major trauma centres.”