The town sits at the junction of several highways - the northern road to Kontum and the highway west to Stœng Trêng in Cambodia.

Pleiku is served by Pleiku Airport in the near outskirt of the city.

It was strategically important during the Vietnam War because it was the primary terminus of the military supply logistics corridor extending westwards along Highway 19 from the coastal population center and port facilities of Qui Nhon. Additionally, its central location on the plateau, between Kontum in the north, and Ban Me Thuot to the south, and the North Vietnamese Army's base areas in Cambodia to the west made Pleiku the main center of defense of the entire highland region of the Republic of Vietnam.

This was strategically obvious to both sides; the U.S. established an armed presence very early in the conflict at Camp Holloway, and the Vietcong attack on this base in early 1965 was one of the key escalating events of the conflict.

After the fall of Ban Me Thuot in early 1975, and the insecurity of Highway 19 leading from Qui Nhon, President Thieu ordered the hasty evacuation of Pleiku. This military operation to attempt the withdrawal of ARVN forces down the ill-maintained tertiary road LTL-7B through Cheo Reo to Tuy Hoa led to a horrific catastrophe of over a hundred thousand evacuees from the Pleiku and Kontum areas killed or stranded without support.