The Metropolitan Police says it will merge all of its policing boroughs in a bid to save £325m by 2021/22.
The current 32 borough model will be condensed to 12 Basic Command Units (BCU) made up of two or three boroughs.
The force warned its numbers are due to fall to 30,000 by April, but said the BCU move will "improve efficiency".
Sadiq Khan blamed government spending cuts for forcing police numbers down, however, critics argued he is "gambling" with Londoners' safety.
The Met said the scheme will be phased in over the next 12 months, meaning officers will cover lager areas.
Each BCU will be led by a Ch Supt who will become the BCU Commander.
Examples of new BCUs include Croydon, Bromley and Sutton merging; as well as Lambeth and Southwark coming together.
Deputy Assistant Commissioner Mark Simmons the BCU structure will allow the Met "to put first victims of crime and those people who need us the most".
He added: "Our new structure will also give us the resilience and consistency we need across the whole of London, so we can continue to respond to large scale incidents and meet the financial and operational challenges we are facing."
Steve O'Connell, who is the London Assembly's chair of the police and crime committee, said the trial was "inconclusive in its effectiveness."
He added: "In rolling out these major changes all at once, there is a risk lower-crime boroughs will be neglected and satisfaction levels with our police service could decline."
Mr Khan argued that the Met's decision was being "driven" by Government cuts to the force's budget, but said the BCU model has been "designed with Londoner's safety as the absolute priority".
"The new units will be designed for every area of London in order to meet the needs of local people and tackle local priorities," the mayor said.
In response to Mr Khan's claims, the Home Office said in a statement: "The mayor is accountable to the London public for police performance and is empowered to raise the precept to increase funding for the Metropolitan Police by around £43 million.
"The Metropolitan Police will receive £2.5 billion in direct resource funding in 2018-19, of which over £1.9 billion is government funding and £634 million from the precept if maximised.
"The Met also has £240 million of reserves to cover unexpected costs and invest, for example, in better technology."
The 12 Basic Command Units (BCUs):
- Hammersmith and Fulham, Kensington and Chelsea, Westminster,
- Kingston, Merton, Richmond, Wandsworth
- Bromley, Croydon, Sutton
- Bexley, Greenwich, Lewisham
- Barking and Dagenham, Havering, Redbridge
- Ealing, Hillingdon, Hounslow
- Lambeth, Southwark
- Enfield, Haringey
- Hackney, Tower Hamlets
- Camden, Islington
- Barnet, Brent, Harrow
- Newham, Waltham Forest