The flight, which will operate three times a week, is the third confirmed by Australia’s newest long-haul airline, which is part of the Virgin Blue Group.
Brett Godfrey, Virgin Blue Group chief executive officer and co-founder, said that passengers had been "crying out" for a new flight on both sides of the Pacific Ocean.
"Even in these tough economic times passenger traffic through Melbourne has been continuing to grow, so stimulating the destination further with more convenient, value-for-money, freshly innovative and high quality air services can only be a good thing for all," he said.
The 36-seat Boeing 777-300ER aircraft will operate on the flight, which features in-flight bars, mood lighting and cutting edge entertainment.
V Australia will introduce a new flight from Brisbane to the Californian city on March 1st.
The airline’s first flight from Sydney to Los Angeles took off on December 15th.