South Flank, Australia's biggest iron ore mine in more than a century, achieved first production in May last year and is ramping up to 80 million tonnes per annum.
The mine was launched with an autonomous-ready fleet.
Under the transition, South Flank is expected to have up to six Komatsu trucks converted to the autonomous haulage system in June.
The trucks will initially be remotely operated from site prior to transitioning to BHP's Perth office.
All 41 haul trucks are scheduled to be operated autonomously within 18 months.
"The transition to autonomous haulage at South Flank will build on the success at Jimblebar and Newman East which have reached new benchmarks in safety and productivity since they adopted fully autonomous fleets," Western Australian Iron Ore asset president Brandon Craig said.
"This is an exciting announcement for WAIO and the South Flank workforce and is expected to result in significant safety and efficiency improvements as well as new job and growth opportunities."
BHP expects the move to create 60 new roles.
The company said automation had improved safety, with the number of near-miss events at Jimblebar and Newman East down 90% since the implementation of autonomous haulage and recordable injuries down 70% at Newman East.
South Flank will be BHP's fifth Australian mine site to introduce autonomous haulage and its third site in Western Australia.