Open to the public from Sunday, "Treasures from the Wreck of the Unbelievable," plunges visitors into a fantasy universe raised from the depths of the Indian Ocean that has been ten years in the making.
And as ever with the 51-year-old Briton, famed for his stuffed sharks and the huge fortune he has amassed as the most commercially successful member of the Young British Artist (YBA) movement of the 1990s, it is nothing if not controversial.
Depending on which critic you listen to, the vast exhibition spread across the Palazzo Grassi and the Punta della Dogana halls of Venice's old customs house, the monumental new collection is either a spellbinding return to form, or a career-ending artistic shipwreck.
In the former camp is the Guardian's Jonathan Jones, who wrote that with the ensemble of more than 200 new pieces, "the arrogant, exciting, hilarious, mind-boggling imagination that made (Hirst) such a thrilling artist in the 1990s is audaciously and beautifully reborn."
Others were equivocal. "A fantasy too far?" asked Jan Dalley in The Financial Times, predicting that visitors would find Hirst's watery fantasy "either fascinating and enriching or pointless and annoying."
And some were damning. The London Times's Rachel Campbell-Johnston, a self-described Hirst aficionado, wrote: "This show is, quite frankly, absurd. It should be dumped at the bottom of the sea."
The two-site exhibition asks visitors to buy into a back story about Hirst being alerted to a shipwreck discovered off eastern Africa in 2008 and organising the recovery of the treasures it contained.
It is these precious coral- and seaweed-encrusted artefacts from the hold of the "Apistos" (Unbelievable), that make up the exhibition.
The ship supposedly belonged to a former slave who amassed a fortune and spent it collecting artefacts across the ancient world: Egyptian sphinxes, Greek statues, and jewel-studded sculptures including a massive 18-metre-tall (60-foot) monster, along with many other gems.
As visitors make their way through the collection they can watch videos of divers carrying out the supposed salvage operation.
But there are many surprises along the way which will unsettle anyone who goes along with the shipwreck story.
From an Egyptian goddess who looks uncannily like Kate Moss to coral-encrusted fossils of Disney characters, it's all about the real and the false. Or as many reviewers saw it, Hirst's take on the very contemporary issue of fake news.
"The visitor does not really know if the works she sees have spent 2,000 years at the bottom of the sea or if they are the work of the artist," said Martin Bethenod, director of the two venues, both of which are owned by the Foundation Pinault, owned by French fashion tycoon Francois Pinault, a noted collector of Hirst's work.
"There is this ambiguity which leaves space for dreams," Bethenod told AFPTV. "There are different levels of interpretation that overlap, which give the project its richness and complexity."
Hirst rose to fame as the leader of the YBA gang that dominated the British art scene in the 1990s.
He won the Turner Prize in 1995 and attracted a huge following that went well beyond the rarified confines of conceptual art.
His 2012 show at Tate Modern in London attracted a record 463,000 visitors at the time to see works including a diamond-encrusted human skull called "For The Love Of God".
He figures regularly on lists of Britain's wealthiest people, thanks partly to a 2008 auction at Sotheby's which saw him cut out the gallery middlemen to sell 223 new pieces for 111 million pounds (130 million euros or $138 million at current exchange rates).
That sale coincided with the start of the financial crisis which hit the contemporary art sector hard, and the value of Hirst's work has waned since.
That has led to much debate about whether collectors will show much enthusiasm for his latest collection.
All the pieces, some of which exist in three different forms, are to be sold after the exhibition ends on December 3rd.
The art world is already busy speculating how much money Hirst will have left after he has covered the huge costs of creating the works over the past decade and transporting them to Venice.
By Franck Iovene and Angus MacKinnon