The Metropolitan Police said detectives had received a dossier of evidence about suspicious activities at the News of the World in 2005 and 2006, and a new team would carry out the probe.
The decision was made after the newspaper handed over material gathered during an internal investigation into its assistant editor Ian Edmondson.
The newspaper said Edmondson was sacked as a result of the investigation.
Edmondson was suspended from duty in December after he was linked to the scandal in documents relating to legal action by actress Sienna Miller lodged at the High Court.
Revealing the new probe, a police spokesman said: “The Met has received significant new information relating to allegations of phone hacking at the News of the World in 2005/06. As a result, the Met is launching a new investigation to consider this material.
“This work will be carried out by the specialist crime directorate which has been investigating a related phone hacking allegation since September 2010.”
The new inquiry is one of the most significant developments in the controversy since the News of the World’s royal editor was imprisoned in 2007.
Clive Goodman and private investigator Glenn Mulcaire were jailed at the Old Bailey after they admitted intercepting messages.
The pair used mobile phone numbers and secret codes to hack into voicemails of celebrities and other high profile people.
Until now the Met has batted away calls for a new inquiry despite a steady flow of people also claiming to be victims of the scam.
However, acting commissioner Tim Godwin and director of public prosecutions Keir Starmer recently announced that lawyers would review existing evidence.
In the statement, the Met said: “Discussions have taken place with the director of public prosecutions in relation to the recently announced role of Alison Levitt QC. It has been agreed that her task will continue and she will evaluate any new evidence and advise as to the progress of the investigation.
“The original phone hacking investigation was undertaken by the counter terrorism command in specialist operations.
“However, in view of their current workload and the continuing ‘severe’ threat level, it has been agreed that it is no longer appropriate to divert them or acting deputy commissioner John Yates from their main duties and responsibilities. This new investigation will be led by deputy assistant commissioner Sue Akers from the specialist crime directorate.”
Last week, Downing Street communications chief Andy Coulson resigned, claiming the ongoing clamour was poisoning his work.
Coulson was editor of the News of the World when Goodman was charged and stepped down the day he was jailed.
News of the World owners News International said in a statement: “Mr Edmondson was suspended in December 2010 following a serious allegation. Material evidence found during the course of the subsequent investigation has led to Mr Edmondson’s dismissal.
“News International has informed the police, handed over the material it has found and will give its full co-operation going forward.
“News International reiterates that it will take swift and decisive action when we have proof of wrongdoing.”