Created in the state redistribution of 3 September 1984, the division is named after Helen Mayo, a social activist and the first woman elected to an Australian University Council.

Taking in the Adelaide Hills, Fleurieu Peninsula and Kangaroo Island regions, its largest population centre is Mount Barker.

Its other population centres are Aldgate, Bridgewater, Littlehampton, McLaren Vale, Nairne, Stirling, Strathalbyn and Victor Harbor, and its smaller localities include American River, Ashbourne, Balhannah, Brukunga, Carrickalinga, Charleston, Cherry Gardens, Clarendon, Crafers, Cudlee Creek, Currency Creek, Delamere, Echunga, Forreston, Goolwa, Gumeracha, Hahndorf, Houghton, Inglewood, Kersbrook, Kingscote, Langhorne Creek, Lobethal, Macclesfield, McLaren Flat, Meadows, Middleton, Milang, Mount Compass, Mount Pleasant, Mount Torrens, Mylor, Myponga, Normanville, Norton Summit, Oakbank, Penneshaw, Piccadilly, Port Elliot, Second Valley, Springton, Summertown, Uraidla, Willunga, Woodchester, Woodside, Yankalilla, and parts of Birdwood, Old Noarlunga and Upper Sturt.

[1] At its creation in 1984, Mayo was a rural electorate that stretched from the seaside town of Victor Harbor to the Adelaide Hills, which had previously been represented mostly by the seats of Barker and Boothby.

Then-Democrats leader Janine Haines chose to contest the neighbouring Division of Kingston at the 1990 election, obtaining a 26.4 per cent primary vote, but came third well behind the Liberals, with sitting Labor member Gordon Bilney retaining the seat.

A redistribution following the 1990 election shifted the Fleurieu Peninsula and Kangaroo Island to Barker, where they had been prior to the creation of Mayo.

[3] NXT's candidate in Mayo was former Briggs staffer Rebekha Sharkie, who is associated with a wide range of organisations in the Adelaide Hills.

[4][5] Multiple seat-level opinion polls in Mayo found NXT surprisingly leading the Liberals on the two-candidate vote during the 2016 election campaign.