The QPR player will make his international comeback after recovering from the broken leg he suffered in an FA Cup tie against Blackburn early in the year.
Mackie is likely to start on a wide position in a 4-5-1 formation with Barry Robson on the opposite flank.
Kenny Miller returns up front after missing the last three internationals through suspension and injury.
His Cardiff team-mate, Don Cowie, lines alongside Darren Fletcher and James Morrison in central midfield.
Allan McGregor starts in goal and there is only one change to Craig Levein's regular back four from recent matches, with Steven Whittaker replacing the injured Alan Hutton at right-back.
Levein named his team on Friday morning after Phil Bardsley and Fletcher trained with the group for the first time on Thursday following minor fitness issues.
Mackie's return came after the Scotland manager was forced to do without a host of midfielders. Scott Brown, Charlie Adam and Graham Dorrans are injured, James Forrest was recalled to the Under-21s for their crucial European qualifier against Holland, and Barry Bannan was left out following his recent arrest on suspicion of drink-driving.
Levein is planning to hand debuts to several players if the game goes his team's way, with Blackpool goalkeeper Matt Gilks and Huddersfield striker Jordan Rhodes both in line to play.
Scotland team to face Cyprus: A McGregor, S Whittaker, P Bardsley, C Berra, G Caldwell, D Cowie, D Fletcher, J Morrison, K Miller, J Mackie, B Robson.
Source: PA
Source: PA