Tina Weaver, Piers Morgan's deputy during his editorship of the Daily Mirror, has been arrested by detectives from Scotland Yard's Operation Weeting inquiry into alleged phone hacking.
In addition, The Sunday People's James Scott has become the first serving editor to be arrested over alleged phone hacking.
Detectives arrested a total of four former Sunday Mirror journalists in dawn raids on suspicion of conspiracy to intercept voicemail messages.
Scott, previously deputy editor of the Sunday Mirror, was held along with the paper's former editor Tina Weaver, 47, a member of the Press Complaints Commission. The paper's current and former deputy editors Nick Buckley and Mark Thomas were also arrested.
The Metropolitan Police said the alleged conspiracy mainly concerned the Trinity Mirror-owned Sunday Mirror between 2003 and 2004 as it announced a fresh element of its major phone hacking inquiry.
Weaver served as Morgan's deputy until 2001, before taking the helm at the Sunday Mirror. The CNN host was editor of the Labour-leaning Daily Mirror from 1995-2004, when he was fired after authorising the newspaper's publication of photographs allegedly showing Iraqi prisoners being abused by British Army soldiers. Within days the photographs were shown to be crude fakes.
Morgan, who gave evidence to the Leveson Inquiry into press standards, has insisted there was no phone hacking during his editorship.
This is the first time Weeting detectives have made arrests in connection with the Mirror. The investigation has previously focused primarily on News International, publisher of the now-defunct News of the World.
The names of the journalists arrested were confirmed by Trinity Mirror, owner of the Sunday Mirror and People. A company spokesperson said: "We take any allegation against employees very seriously and are co-operating with the police".
Scotland Yard said these latest arrests primarily concern the Sunday Mirror's activities between 2003 and 2004, and are being treated as separate from the two strands of investigation involving News International.
The Metropolitan Police said officers would be "making contact with people they believe have been victims of the suspected voicemail interceptions" in due course.
It added: "Detectives on Operation Weeting have identified and are investigating a suspected conspiracy to intercept telephone voicemails at Mirror Group Newspapers.
"It is believed it mainly concerned the Sunday Mirror newspaper and at this stage the primary focus is on the years 2003 and 2004."