The Metropolitan Police were called to Broadway in Stratford shortly after 3pm on Thursday following reports of a stabbing.
The male was pronounced dead at the scene at 3.49pm by medics from the London Ambulance Service, which dispatched an air ambulance.
A second male was found with stab injuries and taken to an east London hospital.
His injuries are not said to be life-threatening.
Scotland Yard said the murdered teenager’s next of kin have not been informed and formal identification is yet to take place.
The force said no arrests have been made and enquiries are ongoing.
A blue and white police forensic tent was set up in front of an entrance to the Stratford Centre, which appeared to have been closed by police.
A witness told the Press Association the attack happened outside a McDonald's restaurant next to the entrance.
“At that moment there were not many people around him so I could see him all covered in blood. He was in pain and tried getting up,” they said.
“There were people around gathering. It was scary as you did not know if any of them could have had a knife too.”
Forensic officers in blue boiler suits can be seen within the cordon.
One stall worker told the PA news agency he had been at a cafe in the centre when he saw police arrive.
He said he saw paramedics trying to perform first aid to a “young guy”.
“I saw police around here and one person was on the floor, I think they stabbed him,” he said.
“It was a young guy. He was a black guy on the floor. I think the ambulance guys tried to give him first aid.”
Uniformed officers manned the barriers while a number of squad cars remained in the area.
Tuc Meral – who owns the Olive and Lemon bistro on Broadway – told the PA he was closing his restaurant early on Thursday as they were within the street cordon.
He said officers had told him they expected it to remain in place until midnight following the fatal stabbing.
Asked about police presence in the area, Mr Meral said: “I always request extra police officers behind here, because there’s some anti-social behaviour.”
A section 60 order, giving officers the power to stop and search in the area, has been implemented.