The England international has been a key player for City this season, featuring in a variety of positions and popping with crucial goals to keep them in the title race.
Most recently he struck in the final minute of their match with Hull City to earn a 1-1 draw and netted the second in a 4-1 win over Stoke City at the Britannia Stadium.
However, manager Manuel Pellegrini confirmed Milner is now set for an enforced absence.
"The only player who has a problem is Milner," said Pellegrini. "He has a problem in his knee and he will not be available.
"It's not very, very serious but he couldn't work all week. All of the other players are fit."
One player Pellegrini will have available is new signing Wilfried Bony.
The Ivorian has yet to feature since moving from Swansea City due to international duty at the Africa Cup of Nations, but he will be involved against Newcastle.
"Bony is an important player," added the Chilean. "He's on the squad list.
"We'll see if he starts or if he's on the bench."
