Cardiff will be C and then A-O for second letter, Glasgow will be S and then A-J and Birmingham will be B then A-Y.
The new plates will also be easier to read and memorise than the existing format, said transport minister Lord Whitty.
Which area of the UK a vehicle comes from will be highlighted via a two-letter regional identifier.
The system for the new number plates - whose format is AB12 CDE - is two letters to identify the region, followed by two numbers to represent the year, followed by three random letters.
The region is represented by the first letter, such as A for Anglia, and the second letter narrows it down further to identify which DVLA office in that region the car was registered at.
There are up to five such offices per region, and each has a range of letters to identify it.
For example, cars registered at the Peterborough office in
Anglia will take letters in the range A-N for the second letter on their number
plate.
Cardiff will be C and then A-O for second letter, Glasgow will be S and then A-J and Birmingham will be B then
A-Y.
"This is good news for motorists and good news for crime-fighting," said Lord Whitty.
"Number plates should be easy to read and easy to remember.
"The new format includes regional and age tags. This will mean that people can identify with their locality.
"They can also help the police by remembering just one or two letters or numbers."
Speed cameras
The new system will also enforce a standard style of lettering to make sure number plates can be better read by speed cameras.
Backing the changes, Edmund King, executive director of the RAC Foundation, said: "We welcome these regulations. They are needed to deter those who seek to obscure their registration mark to cameras.
The AA has also expressed support for the introduction of these new regulations.
And Deputy Chief Constable of North Wales Police, John Owen said: "The police welcome these new regulations.
"There are times when the ability of a witness to identify a vehicle is vital in bringing offenders to justice.
"It is therefore essential that number plates are easy to read."