Already guaranteed to end the year as world number one after winning Wimbledon and the U.S. Open, Djokovic is a massive favourite to complete an incredible resurgence from world number 22 in June with another title in London's docklands.
Novak Djokovic is undefeated and leads his group with two wins, four sets and a total of 24 games won while conceding 12.
Isner, who at 33 became the season-ending tournament's oldest debutant since 1972, applied himself admirably but barely avoided being broken a couple of times in the first set, and was broken twice more in the second set.
And it proved to be not a very different match, although a slightly below par Djokovic, still apparently carrying the cold virus from Paris, had to dig deep in the latter stages of the first set as a calm and confident Zverev pressed him hard in long baseline rallies.
"He obviously made a lot of unforced errors that allowed me to win, probably easier than expected. I kind of enjoyed the time off but I missed this arena and I'm glad to be back". Djokovic saved it with a service victor but then double-faulted to give the 21-year-old another opportunity.
Zverev has hired eight-time grand slam champion Ivan Lendl in a move to get him to the next level and Djokovic believes that is a sound move that will pay dividends.
"Djokovic beat Zverev in straight sets in his second round ro" pundit and former British No 1 Greg Rusedski.
Despite his hopes having gone, Isner stuck to his task in the second set but Zverev, still needing the victory to make sure of his semi-final berth, powered to his 56th win of the year.
Isner double-faulted to hand Cilic a decisive break in the eighth game of the second set and then did the same to gift Cilic a break at the start of the third.
The Croatian fifth seed had lost nine of his previous 10 matches at the Finals, and he looked in danger of another letdown when he dropped the first set against Isner. 'The very best can play that sort of style for four hours. "John is such a tough opponent, the first set was unbelievably tight so I'm just happy to be through". But I came up with some great shots in the tiebreak as well. Zverev did not break Djokovic's serve once throughout the 76-minute match.