The Grand Tour was inspired by an 18th Century tradition where the wealthy toured Europe's cultural sites.
Nottingham Contemporary, Chatsworth House, Derby Museum and The Harley Gallery are all taking part.
It is hoped a number of exhibitions, which run until September, will increase visitor numbers at the venues.
The two counties have been chosen due to their connections to the original grand tours, which helped shape the art collection at Chatsworth, in Derbyshire, and The Welbeck Estate, in Nottinghamshire.
Much of Chatsworth's collection was amassed by the Dukes of Devonshire. Items were either collected during the tour or were inspired by what had been seen.
Local figures like Lord Byron, whose ancestral home is Newstead Abbey, would have also taken part in the tour.
At Nottingham Contemporary, artist Pablo Bronstein will display hand picked objects from Chatsworth House's collection, including works by Rembrandt and Frans Hals.
A colossal Roman marble foot from the stately home will also be on display in Nottingham.
In Derby, The Wright Revealed exhibition focuses on two rare paintings by 18th Century painter Joseph Wright.
One of the paintings languished in a museum store room for more than 50 years.
The Grand Tour project has been co-funded by the National Lottery and the Arts Council to help create cultural destinations around the UK.

"I love writing, cooking and baking. I'm enjoying what I'm doing and I don't want it to be taken away from me," the Junior Bake Off judge told the BBC.
When asked if Channel 4 had approached her about the show, which is moving from BBC One, she told Newsround: "No."
Channel 4 signed a three-year deal earlier this month with Love Productions, which makes the programme.
But judge Mary Berry will not move after she quit The Great British Bake Off last week out of loyalty to the BBC, a few days after presenters Mel Giedroyc and Sue Perkins also decided not to make the move to Channel 4.
Paul Hollywood is the only Bake Off star to have agreed to stick with the show and switch to Channel 4, so there is speculation as to who will present and judge the show.
It was announced last month that Hussain, who won in 2015, was to judge the CBBC junior version of the show, alongside chef and food writer Allegra McEvedy.
Channel 4 will begin airing the programme in 2017, starting with a celebrity special in aid of Stand Up To Cancer.
Hussain was asked by BBC Breakfast about her views on Bake Off changing channel, but responded by saying: "It's old news.
"Change happens, change comes, wherever it [the show] goes I just want it to do well, whatever happens, wherever it goes."
But when asked about the importance of Mel Giedroyc and Sue Perkins to the show, she said: "Mel and Sue are so important to the show. Every time I was falling apart they'd come and say, 'It's just cake, come on you can do this.'"
She added it is "the least competitive competition in the world" and that "you like each other, there's camaraderie in the competition, you don't see that anywhere else."
She said: "You want to win and do really well and you want everyone to do well as well."
The BBC and Channel 4 clashed over Bake Off on Tuesday at the Royal Television Society London Conference.
James Purnell, the BBC's director of strategy and education was in a debate with Channel 4's chief creative officer Jay Hunt.
Hunt said: "I understand that you feel aggrieved about Bake Off although it is worth remembering the BBC lost Bake Off. Channel 4 didn't take Bake Off."
Purnell told her: "You have a remit which you describe yourself as 'born risky'. I think there's real questions about whether buying Bake Off qualifies for that."
The Great British Bake Off began life on BBC Two in 2010, where it became a firm favourite with viewers before moving to BBC One in 2014.
Last year's final was the UK's most watched television programme of the year, with 13.4 million viewers tuning in to see Hussain win the competition.
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A £350,000 project is set to link four cultural venues across Nottinghamshire and Derbyshire in a bid to increase tourism and boost the local economy.
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Great British Bake Off winner Nadiya Hussain said she has had "no offers" from Channel 4 to join the show.