Major industries are agriculture, fisheries, public services (particularly health) and tourism; the region is also popular for niche crops, hobby farmers, and retirees from life in the larger cities.

The major towns of the area developed at the navigable heads of the local river systems (Murwillumbah on the Tweed, Lismore on the Wilsons – a tributary of the Richmond – and Grafton on the Clarence) rather than on the coast, in order to be able to transport the valuable timber products (in particular the Australian red cedar, Toona ciliata) to markets interstate and overseas.

[6] Ballina is a fishing port and was a centre for Australia's east coast offshore prawn industry, although boat numbers have declined in recent years, while additional vessels operate out of Iluka and Yamba.

The village of Nimbin, in the Lismore area, also attracts tourists interested in its reputation for environmental and alternative living initiatives such as permaculture, sustainability, and self-sufficiency, as well as its often-cited counterculture which includes lobbying for the decriminalisation of recreational and medicinal cannabis, as evidenced by its annual MardiGrass celebration.

[12][13][14][15] Prior to European settlement in the nineteenth century, the region was home to the Aboriginal Bundjalung people (or Bandjalang) (including the Widjabul of the Lismore region, the Arakwal of the Byron Bay area, and the Kalibal and Minjungbal of the Tweed and Queensland border) and the Gumbaynggirr and Yaegl peoples to the south, which collectively still form a component of the local population,[16][17] and have been successful in some native title land claims on behalf of local Bandjalang and Yaegl communities.

The locality of New Italy was settled in 1882 by Italian pioneers who attempted to cultivate the area's difficult interior, while additional phases of migration followed in the 1920s and again with the post-World War II influx of European migrants anxious to escape their war-ravaged country.