Djokovic is the favourite to win the tournament and he kicks-off his campaign against the lowest ranked player in the competition.
World No 10 Isner qualified for the season-ending event for the first time in his career because Rafael Nadal and Juan Martin del Potro withdrew through injury.
However, the American was in good spirits ahead of his daunting debut, even joking that he would make light work of the world No 1.
“I think it will be really easy for me,” Isner said.
“He is the number one player in the world and he has won this event five times if I am not mistaken.
“He is the player to beat this week for sure. He is back to number one in the world and the second half of the year has been a whirlwind.
“It is a good spot for me because I don’t have much to lose. I am definitely the underdog.
“I have got to go out there and try my best, try to play loose and free and see what happens.”
Novak Djokovic vs John Isner LIVE – 8pm start
8pm: The lights have been dimmed, dramatic music is blasting and the players are heading to centre court right now!
7.45pm: Bang on queue the doubles tie is over with Mike Bryan and Jack Sock taking home the victory.
Now the excitement is really beginning to build ahead of Djokovic vs Isner.
How will the Serbian handle the towering American’s serve?
Stay tuned to find out…
7.30pm: A little birdie has told me that Cristian Ronaldo is in the house tonight to take in the action.
I wonder who the Juventus forward will be supporting in the main event?
7.15pm: The crowd here in the O2 Arena are still being entertained by this gripping doubles match between Lukasz Kubot / Marcelo Melo and Mike Bryan / Jack Sock.
This one is close to the end of the second set and should be wrapped up in the next 15 minutes at the latest.
And then we will be waiting for Djokovic and Isner to make their way into the main arena.
A quick reminder of what happened earlier in the day in Group Guga Kuertens: Alexander Zverev beat Marin Cilic 7-6(5), 7-6(1).
7pm: Good evening and welcome to Djokovic vs Isner live from the O2 Arena in London.
Djokovic is the clear favourite to win the tournament after cementing his place as the year-end world No 1 – a trophy he was awarded yesterday.
Isner is making his debut here and will become the tallest player to ever compete at the ATP Finals at 6ft10.
You would expect Djokovic to wrap this one up in straight sets, but after Federer lost to Nishikori last night, you can never rule the underdog out…
