It will look into claims of perverting justice and perjury after 900 sub-postmasters were wrongly convicted.
They were prosecuted over accounting shortfalls despite known problems with the Horizon computer system they had to use.
The probe will focus on bosses at both the Post Office and tech giants Fujitsu.
It will be split into four regions and given similar resources to a major terrorism investigation.
At least 20 potential suspects have been identified, but more could follow.
But any charges will not be brought until after the current public inquiry — possibly as late as 2026.
The Met Police has been heading a preliminary inquiry since 2020.
Commander Stephen Clayman said detectives had been “working through millions of documents”.
Former postmistress Cheryl Shaw told The Sun: “It’s a relief to see that justice could be served.”
Senior executives in the Post Office and Fujitsu have denied wrongdoing.