Officers found a 15 year old boy with stab wounds on Stratford Broadway, east London, shortly after 3pm on Thursday.
Police believe he was either attacked on a bus, or shortly after getting off. A second teenager, also 15, was found with stab injuries which are not believed to be life threatening. Scotland Yard said no arrests had been made.
The boy died shortly after the attack.
Det Ch Insp Chris Soole said the boy was stabbed during a fight “on or shortly after alighting from a bus which stopped very close to Stratford Shopping Centre”.
He added: “The victim of this stabbing was a schoolboy with his whole life ahead of him. He had everything to live for.
“This was a senseless attack and we share the concern and alarm this murder will no doubt cause in the local community.”
In a separate stabbing about five hours later, an 18 year man was knifed to death in south London. Police found the man suffering from stab injuries on the Brandon Estate in Camberwell, at about 8.20pm. He died at the scene an hour later and no arrests have been made.
Police said the Stratford victim’s friends and members of the public provided first aid but he died at the scene at about 3.50pm.
The teenager’s next of kin have been informed, and the second boy who was stabbed remains in an east London hospital.
