Steve Clarke's side are looking to build on their Euro 2020 qualification when they run out at Hampden.
Here the PA news agency looks at the major talking points ahead of the game.
Clarke has admitted being tempted to move Scott McTominay into his natural midfield role after deploying him in the back three during the autumn. The 24-year-old has scored six goals for Manchester United in the past four months. An injury to Rangers midfielder Ryan Jack plus the return of centre-backs Grant Hanley and Jack Hendry gives Clarke scope to push McTominay further forward.
With Scotland only scoring three times in the past 10-and-a-half hours of action, Clarke has introduced Southampton forward Che Adams and Hibernian striker Kevin Nisbet to his squad. Lyndon Dykes is the man in possession of the number nine jersey and he ended a four-month goal drought by netting for QPR at the weekend. But there could well be at least one debut as the game progresses.
Who will draw first blood?
The last time Scotland qualified for the World Cup, they opened their campaign with a goalless draw in Austria before beating their opponents 2-0 at Celtic Park. Both teams qualified for the 1998 finals but have never made it since, partly because doing so has become more difficult in Europe. Only the top team is guaranteed entry to Qatar 2022 and the opening game already looks a crucial one for both teams as Denmark are the top seeds.