The visitors have picked up 16 points after an impressive start to their qualifying campaign and an away victory would put them in pole position to top the group.
Andorra have only won one game out of their six matches so far, a victory against rock-bottom San Marino, and the England boss may well field a weakened team as he did in the reverse fixture back in September.
Here's everything you need to know before Saturday's match:
Southgate announced his squad for the two upcoming games last Thursday, and for the most part, it is full of familiar faces.
— England (@England) September 30, 2021
Another three players who were in the last squad but didn't make the cut this time are Nick Pope, Jude Bellingham and Patrick Bamford – yet their absence has freed up room for other players to force their way into Southgate's plans.
Goalkeepers: Sam Johnstone (West Brom), Jordan Pickford (Everton), Aaron Ramsdale (Arsenal)
Defenders: Conor Coady (Wolves), Ben Chilwell (Chelsea), Tyrone Mings (Aston Villa), Luke Shaw (Manchester United), John Stones (Manchester City), Fikayo Tomori (AC Milan), Kieran Trippier (Atletico Madrid), Kyle Walker (Manchester City)
Andorra: Gomes, San Nicolas, Llovera, Vales, Garcia, Rubio, Rubio, Viera, Rebes, Clemete, Sanchez
England: Ramsdale, Trippier, Tomori, Mings, Chilwell, Ward-Prowse, Henderson, Foden, Lingard, Saka, Watkins
One to watch:
Many were unsure whether the 28-year-old could rekindle his Old Trafford career despite an impressive loan spell at West Ham last season, but the versatile player has silenced the doubters.
Lingard scored a delightful goal after coming on off the bench against Newcastle and repeated his heroics against The Hammers themselves with a last-minute winner to break the hearts of the fans who grew to love him last season.
Staying in Manchester and not being guaranteed first-team football looked like it could hinder his chances of being called up again to play for England, yet his resilience and performances since the summer have left Southgate with no option.
Lingard also scored two of England's four goals the last time they faced Andorra, so we should perhaps expect him to shine once more.
Head to head:
The two sides have only faced each other five times but England have been victorious on every occasion.
More impressively, The Three Lions haven't conceded a goal in those five matches, whilst they have found the back of the net 20 times, averaging four goals a game.
How to watch:
The 19:45 BST game will be broadcast on ITV 1 from 19:00 BST and match highlights will be available on Youtube and ITV Hub shortly after the full-time whistle.