Jose Mourinho finds himself under mounting pressure after a run of four games without a win, with last weekend's shock 3-1 defeat at West Ham leaving his side nine points off the top of the league in 10th place.
Having not gone five matches without victory since December 2015, they are 47/100 (1.47) favourites with William Hill to return to winning ways in this one.
Also in dire straits after picking up just two points from the opening seven league games, the Magpies are available at 6/1 (7.00) to get their season up and running with a shock win here.
Each of the last three fixtures at this ground have resulted in a draw, and you can get odds of 10/3 (4.33) on this one also finishing up all square.
Salomon Rondon is ruled out due to a thigh injury, while DeAndre Yedlin, Frederico Fernandez and Paul Dummett all face late fitness tests.
Although fans are not quite calling for the manager's head, there were audible boos following the frustrating goalless stalemate against Valencia.
While they have never really set pulses racing under Mourinho, the Red Devils have looked particularly uninspired and ponderous in recent matches - scoring just three times in their last four home games.
Having put in determined defensive performances in narrow defeats to Tottenham, Chelsea, Manchester City and Arsenal already this campaign, Rafa Benitez's men will back themselves to cause more frustration for the home supporters here.
Considering Newcastle haven't conceded more than twice in any of their seven league matches so far this season but have scored just once in three on the road, odds of 17/20 (1.85) are well worth backing on them holding a struggling Manchester United to under 2.5 goals.