Chris Coleman confirmed that the Madrid man is not yet fit enough to play 90 minutes for the Dragons, and will not be risked at the Phillip II Arena unless he is fully read.
Bale joined the squad in Cardiff on Monday following his world-record 86 million pound transfer to the Bernabeu, but having not played for Tottenham since July, Coleman says he is unwilling to throw his star performer in at the deep end.
Wales' chances may be hampered somewhat as a result, with Bale having scored five of his country's last eight goals, but Coleman will not be taking any chances with the former Spurs man.
"If he is not ready we will not risk him, regardless of whether it is a world record fee," he said. "We are aware a lot of people will want to see him play in the home game against Serbia [on Tuesday].
"But he has no chance of playing 90 minutes on Friday or on Tuesday."
Newcastle United defender Paul Dummett could be in line for a senior debut after featuring for his club side against Manchester City this season, while Cardiff City teenager Declan John is also in the squad for the first time.
Dummett's chances of appearing were boosted as Swansea City left back Neil Taylor was forced to pull out of the squad due to a thigh injury. Joe Allen (hamstring) and Neil Eardley (knee) were also forced to withdraw.
For Macedonia, Aleksandar Todorovski misses out on a place in the squad due to injury, while Stefan Sprivoski has been left out due to a lack of playing time, having failed to feature for his club side, Borac Cacak of Serbia, so far this season.
Central defender Boban Grncarov returns, as do left back Aleksandar Lazevski and attacking midfielder Darko Tasevski.
Macedonia currently sits bottom of Group A, with four points from six matches, two behind fourth-placed Wales, but coach Cedomir Janevski is looking at Friday's game – and Tuesday's visit of Scotland to Skopje – as a chance for his side to earn some points and climb the table.
"Before us are two very important but also difficult games," he said. "It resumes our battle for a better final position in the standings. We do have a chance for the third place and that's a good motive for us.
"Our goal is to move up the table. Wales are a serious team, with exceptional quality and fighting spirit. They have a lot of players from the Premier League so we have to show them respect."