Roger Federer became the first three-time champion of the Cup of Chapman, and Switzerland for the fourth time won the exhibition tournament, second in wins only to team US, which has six titles.
In what is tipped to be the final edition of the unique tournament, the best was saved for last as Federer became the first player to win three Hopman Cups, teaming with Belinda Bencic to make it successive titles in Perth.
Federer and Bencic past year defeated the same German pair of Zverev and Kerber in the final.
Federer and Bencic clinched victory when Zverev hit the ball into the net on the winner-takes-all final point at 4-4 in Saturday's final.
There are doubts over the future of the Hopman Cup with the ATP World Team Cup set to be introduced next year.
Zverev talked of hoping to return next year, and Bencic admitted, "I would love every week to play Hopman Cup!".
After the final point of their mixed doubles match, Sakkari was not any more Federer's opponent, but his biggest fan.
"We really wanted to win as a team", Zverev said.
Jurgen Klopp reacts to Manchester City defeat
City are now back to within four points of table-topping Liverpool and looking to re-establish momentum following an uncharacteristic wobble in December.
The last German victory in the unofficial Mixed championship, which will be replaced by the newly created ATP-Cup, had brought in 1995, Anke Huber and Boris Becker, in 1993, Steffi Graf and Michael Stich had been for the first time for Germany.
Muguruza withdrew from the mixed doubles rubber with a left thigh injury that troubled her during the singles clash and was replaced by American teenager Whitney Osuigwe, ranked 201 in the world, as Spain went down 4-2 4-2.
I played well and served good.
The third set went to a tie breaker with Federer and Bencic winning a thrilling match point. "I'm a bit surprised that the matches have gone as well as they have".
Federer had beaten Frances Tiafoe, Stefanos Tsitsipas, Cameron Norrie and Zverev in straight sets and will be full of confidence heading into Melbourne Park later this month.
When asked if Williams had gifted one back, he said: "No, but that's her choice".
However, Zverev and Kerber returned fire, taking the second set from the Swiss combo 4-1. "I think people, what they enjoy about this competition, is the fact that it's mixed".