Cameron's full day of evidence at the inquiry into media ethics is expected to be dominated by his friendship with ex-News International boss Rebekah Brooks and decision to hire former News of the World editor Andy Coulson as his director of communications.
Robert Jay QC, counsel for the Royal Courts of Justice inquiry, is also likely to focus on culture secretary Jeremy Hunt's handling of the takeover bid for Sky by Rupert Murdoch's News Corporation.
The company launched its £8bn bid for the remaining Sky shares it did not already own in June 2010, but abandoned the move the following summer after cross-party pressure from MPs over the phone hacking scandal at the News of the World.
When Hunt appeared at the Leveson Inquiry last week, it emerged that he had sent a memo to Cameron expressing support for News Corp's bid.
This came ahead of him being handed the quasi-judicial role of deciding over the takeover in December 2010.
Labour yesterday failed in a bid to force Hunt's conduct in the Sky bid to be investigated by the independent adviser on ministerial affairs, Sir Alex Allan.
The prime minister has consistently backed the culture secretary amid calls for Hunt to resign.
Brooks, who appeared in court yesterday on charges of conspiracy to pervert the justice in the police hacking investigation, told the Leveson in her evidence that she exchanged messages with Cameron about once a week while he was in opposition.
The frequency of contact increased in the run up to the 2010 general election, but she claimed that the messages were mostly about social occasions.
Coulson quit as Cameron's communications chief in January 2011, citing the pressure from the emerging coverage of the phone hacking affair.
Cameron will be the sole witness today and he has already submitted his witness statement and evidence of key meetings, emails and texts.