Mitchell Highway also forms part of the shortest route between Sydney and Darwin, via Bourke and Mount Isa, making it an important road link for the transport of passengers and freight for regional New South Wales and Queensland.

At Molong, the highway generally starts to head east towards Orange, where an alternative route diverts many heavy vehicles away from the city centre; the portion of Mitchell Highway that passes through Orange city centre is known locally as Summer Street.

[13] On 5 September 2014, a truck travelling on Mitchell Highway rolled off a road bridge at Angellala Creek approximately 30 km south of Charleville (26°39′15″S 146°10′34″E / 26.6541°S 146.1760°E / -26.6541; 146.1760).

[14] The blast was so powerful that the truck was disintegrated and the dangers posed by the remaining ammonium nitrate necessitated a 2 km exclusion zone around the site for a number of days.

By 7 October, the side track had been upgraded to support road trains, ending the need to detour.

[17] In April 2015, the $10 million tender to reconstruct the highway and bridges were awarded and the construction work took place between June and November 2015.