The producing pair will travel across the country in a private passenger train instead of the typical tour bus for their 'Full Flex Express' tour, which will kick off on July 13 in Toronto.
Canadian singer Grimes, Pretty Lights, KOAN Sound and Tokimonsta are also featured in the six-city tour. Grimes will not be performing on the July 14 show though.
Each show will be set up like a festival featuring multiple stages.
'Full Flex Express' was inspired by two tours that also travelled by train - the 'Festival Express' tour with Janis Joplin, The Grateful Dead and The Band in 1970, as well as last year's 'Railroad Revival' tour with Mumford & Sons and Edward Sharpe and the Magnetic Zeroes.
Dates for the 'Full Flex Express' tour are as follows:
July 13 - Fort York, Toronto, Ontario
July 14 - Ottawa Blues Fest, Ottawa, Ontario
July 15 - Parc Jean Drapeau, Montreal, Quebec
July 18 - Shaw Park, Winnipeg, Manitoba
July 20 - Kinsmen Park, Edmonton, Alberta
July 22 - PNE Coliseum, Vancouver, British Columbia
Skrillex and Diplo along with fellow producer A-Track are also set to remix Michael Jackson's Bad for its 25th anniversary as part of a new Pepsi project.
Skrillex, who recently collaborated with Damian Marley, turned down the chance to perform live with Deadmau5 and Foo Fighters at this year's Grammy Awards, where he took home three awards.
Watch Skrillex's 'First of the Year (Equinox)' video below: