The Blues head North having won their previous six games in all competitions and face a side which suffered defeat to Man City in extra time in the Capital One Cup in midweek.
The Portuguese managed Chelsea in three top flight fixtures at Newcastle during his first spell in charge at Stamford Bridge between 2004 and 2007 but collected just two points from those visits.
However, the former Real Madrid boss is likely to feel upbeat about bucking that trend this time around, as his men head to Tyneside having won their last six games in all competitions.
Chelsea has lost just once in nine Premier League matches this season - the 1-0 reverse at Everton in September - and go into this weekend's encounter joint-second in the table after Fernando Torres' injury time winner gave it a 2-1 win over Manchester City last Sunday.
And with leader Arsenal facing second-placed Liverpool in Saturday's late kickoff, a fourth consecutive league victory could see Mourinho's side finish the weekend top of the pile.
Torres' strike against City was his third goal in his last two games and the Spain international looks set to lead the line once again for the Londoners.
Mourinho made 10 changes for the midweek Capital One Cup win at Arsenal and has no new injury concerns, with Marco van Ginkel [knee] his only long-term absentee.
In contrast to Chelsea's recent form, Newcastle goes into the fixture having won only once in its last five Premier League games.
Alan Pardew's side will be keen to bounce back from the disappointment of losing the Tyne-Wear derby at Sunderland last Sunday but has taken maximum points from just one of four Premier League home games so far this term.
However, Newcastle ran out the victors in the corresponding fixture last term, as Moussa Sissoko's double inspired a 3-2 success over a Chelsea outfit managed by Rafael Benitez.
Pardew will have to overcome something of a defensive injury crisis to repeat that feat, though, as Paul Dummett [hamstring] joins Massadio Haidara [hamstring] and Ryan Taylor [knee] on the sidelines.
Captain Fabricio Coloccini [groin] and Steven Taylor [hamstring] are also doubtful, although Mapou Yanga-Mbiwa returns from suspension after missing the defeat at the Stadium of Light.