[1] Isisford is situated in Central Western Queensland on the Barcoo River, and is approximately 120 kilometres (75 mi) south east of the town of Longreach.

[27] The first Europeans to enter the area were members of the expedition led by Thomas Mitchell, who journeyed through what is now Isisford in September 1846.

[28] In 1847, Edmund Kennedy's exploratory group travelled through the region where he obtained the name of the Barcoo River from an old Kuungkari man living near Yuranigh's Pond.

[30] In 1862, the expedition led by William Landsborough camped close to the same place and likewise felt threatened by the resident Kuungkari.

[31] British pastoralists began to enter the region in 1866 with John Charles Ellis and his brother Evelyn taking up land.

A year later, Charles Lumley Hill established the neighbouring Isis Downs property and John Fanning formed Ruthven.

Punitive expeditions conducted by Native Police and local pastoralists such Charles Lumley Hill subsequently occurred, with many Indigenous people being shot.

[48][49] The Queensland Government called for tenders to build a court house in Isisford in August 1883 with the contract awarded to William McLaughlin in November 1883.

[52] In April 1910, Isisford became the first town in Australia to be serviced by a motorised mail delivery (from Ilfracombe, 90 kilometres (56 mi) to the north).

[54] In the mid-1990s, the first fossils of Isisfordia, an extinct genus of crocodile-like animals, was discovered in a dry creek close to the town.