The force said it was looking into a “confirmed sighting” of the terror suspect by a member of public at Wandsworth Roundabout, under a mile from the prison.
The witness saw a man matching his description climbing out from underneath the delivery lorry he is thought to have strapped himself under.
He was then seen walking into Wandsworth town centre.
The force said it was one of several “key lines” of inquiry being followed in the hunt for Khalife, who had been facing terror charges, as they offered up a £20,000 reward for information leading to his capture.
Met Police counter-terrorism commander Dominic Murphy described the development as potentially “very significant”, and described it as a “confirmed” sighting.
“This remains a fast-paced and dynamic investigation, but I want the public to know that a large number of officers are working extremely hard to locate Khalife,” he said.
“We have now received more than 100 calls from the public, and we thank everyone who has contacted us with information.
“The sighting near Wandsworth Roundabout could be very significant, and this is one of many useful lines of enquiry that officers are pursuing.
“We continue to urge the public to contact us straight away if they think they have seen Khalife or have information on his whereabouts.
“We will continue to work closely with all our colleagues in police services across the country and other partners to trace Khalife and bring him back into custody.”
Officers released new images of the chef’s uniform Khalife is thought to have been wearing when he made his escape, suspected to have been carried out by strapping himself to the underside of a BidFood van.
Police also released new CCTV footage of the route the van took as it made its way out of HMP Wandsworth.
Earlier Friday, officers searched Richmond Park in west London, just over four miles from the prison, in the hunt for Khalife.
Met Police Commissioner Sir Mark Rowley said police are considering whether the escape was an inside job.
The 21-year-old former soldier was being held at HMP Wandsworth while awaiting trial for planting a fake bomb and gathering information that might be useful to terrorists or enemies of the UK.
According to reports, he is accused of gathering information for Iran.
He is accused of eliciting or trying to elicit information that could be useful for a terrorist on August 2, 2021, and breaching the Official Secrets Act by gathering information that could be useful to an enemy between May 1, 2019, and January 6, 2022.