The world No.1 and hot favourite to claim his sixth London title was a comfortable 6-4 6-3 winner over 6ft 10in serving machine Isner at the O2 Arena.
The Serbian is back in business following an injury-hit few months which saw him enter Wimbledon in July ranked No.21 in the world.
But after lifting his fourth SW19 crown and triumphing at the US Open, as well as claiming titles in Cincinnati and Shanghai, Djokovic is once again top of the tree and was presented with the year-end world No.1 trophy on Sunday.
And with a cloud hanging over Roger Federer, who was dreadfully out of sorts in losing to Kei Nishikori on Sunday evening, the path looks clear for Djokovic to move level with the Swiss on six ATP Finals titles.
Isner, at 33 now the oldest debutant at the Finals - Kevin Anderson held that record for just over 24 hours - boomed down his usual missiles, but Djokovic had break points in his first two service games before making one count in his third.
With Cristiano Ronaldo watching from the crowd, Djokovic secured his second break at 3-3 in the second and went on to dispatch Isner with the minimum of fuss.
Djokovic said: "It's great to be back in the 02, it's been a lucky place for me over the years.
"The match was great. I managed to get three breaks of John's serve which is sometimes mission impossible, but I managed to be at the right place at the right time, and I held my serve very well and played solid.
"I missed this tournament last year because of injury. I kind of enjoyed the time off but I missed this arena and I'm glad to be back."
Last year's Wimbledon runner-up went down 7-6 (7-5) 7-6 (7-1) and has now won just one of his 10 matches at the end-of-season tournament - against Nishikori in 2016 when Cilic had already been eliminated.
It was also a sixth straight defeat inflicted upon Cilic by German rising star Zverev, and a lot of it was of the Croatian's making.
Cilic had break points for 4-0 and 5-1 in the opening set but could not take advantage, allowing Zverev to work his way back into the set with a break for 4-5.
Then at deuce Cilic consulted umpire Ali Nili before deciding against challenging a long call which, had he done so, would have earned him set point.
Cilic said: "I asked him if it was out and he showed me that it was out, clearly, so just I didn't - I was not going for a challenge. Even when I hit the shot I felt it was going to be close."
It was hardly the cream of men's tennis. The players had hit just 19 winners between them, and made a combined 46 unforced errors, when Zverev took the set on the tie-break.
In the second set tie-break Cilic was left to rue a wasted challenge earlier in the set which meant he did not have one left to overturn another bad call.
"A few calls like that didn't go my way," added Cilic.
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