The hosts go into this match off the back of a flattering 4-0 win over Malta on Friday, and another victory tonight would leave them on the brink of booking their place in next summer's tournament.
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Just two points separate these two sides at the top of Group F as things stand, and with only one guaranteed place at next summer's World Cup on offer the winner tonight will be in a very strong position to book their place on the plane to Russia. England are in the driving seat at the moment and could move to the brink of qualification with another win here, but defeat leaves them playing catch-up with only two games remaining.
It promises to be a fateful night in Group F, but before we have a closer look at both sides let's first check out the team news...
One of those sees Eric Dier return from suspension in the heart of the midfielder, where he will partner captain Jordan Henderson. Southgate was criticised for playing two defensive midfielders against Malta - with Livermore alongside Henderson for that match - but they are much more likely to be needed tonight against what can be a dangerous Slovakian team.
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The full-back starts again tonight in an unchanged back five for the Three Lions.
The last time they failed to pick up maximum points here was almost five years ago when they drew 1-1 with Ukraine in September 2012.
The Wembley record is certainly daunting, but Slovakia will fancy their chances more than many fo the teams who have visited since their last competitive defeat here.
Only a late goal gave Slovakia and two-goal cushion in their 3-1 win over minnows Malta before they edged past Lithuania in a 2-1 win. Friday's match against Slovenia then looked to be heading for a goalless draw before an own goal nine minutes from time saw Slovakia claim all three points.
This will be a tough game for England - they are not playing particularly well at the moment and have a lot more to lose than Slovakia tonight. However, they do always seem to get the job done at Wembley and I expect them to come out on top once again tonight. It will require an improvement from the hosts, but I'm going for a narrow victory.
England 2-1 Slovakia
That proved to be Sam Allardyce's first and last match in charge of England, and he needed a late Adam Lallana strike to win it exactly one year ago.
ENGLAND STARTING XI: Hart; Walker, Cahill, Jones, Bertrand; Dier, Henderson; Oxlade-Chamberlain, Alli, Rashford; Kane
SLOVAKIA STARTING XI: Dubravka; Pekarik, Skrtel, Durica, Weiss, Nemec, Skriniar, Hubocan, Hamsik, Mak, Lobotka
The Manchester United man tries to dribble his way out from the back but is caught in a dangerous position and Slovakia punish him straight away. A chipped ball over the top finds Lobotka in the box, and he takes the ball down well before stroking it past Hart.
Lovely finish from the Slovakian, but that was very avoidable for England.
The problem for England against Malta was that they struggled to find a way past the deep defence, with 11 players often behind the ball, but today it has been Slovakia who have taken the game to England so far. The opposition playing more should help England, but it has been a slow start from the hosts.
Elsewhere around Europe, Mesut Ozil has given Germany the lead against Norway, while Arkadiusz Milik has broken the deadlock for Poland against Kazakhstan.
Elsewhere, Germany have scored a third through Timo Werner, while Northern Ireland are ahead against Czech Republic through Jonny Evans.
7 - England have conceded at home in a competitive game for the first time in 7 matches, since winning 3-1 v Slovenia in Nov '14. Stun.— OptaJoe (@OptaJoe) September 4, 2017
It is not the best corner from Rashford in truth, but Dier makes something out of it with a clever dart to the front post. He still has a lot to do from that position, but he manages to squeeze his clever shot just under the crossbar, leaving both the defender on the line and the goalkeeper no chance.
Away from Group F, Germany's rout continues as Leon Goretzka has made it 5-0 against Norway in Stuttgart.
Having been at fault for Slovakia's early opener, the Manchester United man now has a goal and an assist to his name, and it is a very good goal too. Rashford is afforded space around 25 yards from goal, and he doesn't need a second invitation to drill a dipping strike right into the bottom corner.
Elsewhere, Kamil Glik has put Poland 2-0 up against Kazakhstan, Montenegro lead Romania and Germany are now six goals to the good against Norway.
It is not a result or a performance which will strike fear into the hearts of teams around the world, but it is another big step towards the tournament in Russia next summer.
Thank you very much for joining Sports Mole for tonight's match as England come from behind to beat Slovakia 2-1 and move five points clear at the top of Group F with only two games remaining. I will leave you with our match report, and be sure to stick around for reaction too.
From me, though, it is goodbye for now!