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.
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.