Witnesses described the plane exploding on impact and erupting into a "massive fireball." There were no fatalities other than those on board the aircraft, police said. The incident happened about an hour before the mall was due to open, according to police.
"There were five people on the airplane and it looks like nobody's survived the crash," Stephen Leane, the assistant police commissioner for Victoria state, told reporters in Melbourne, Australia's second largest city.
Leane said the plane hit the building before crashing into the mall's car park. He described plane as suffering "catastrophic" engine failure, but officials said it was too early to say what caused the accident.
Local media reported the pilot was an experienced aviator in his 60s. The State Department did not identify the four Americans, who were passengers on the plane.
"We extend our deepest condolences to the families and loved ones of all those who died in today's tragic crash," a State Department official told NBC News.
"The U.S. Embassy and Consulate in Melbourne are working closely with local authorities. We stand ready to provide all appropriate consular assistance to the families of the victims," the official added.
Video footage showed burning wreckage strewn across the mall's car park and a thick column of black smoke rising from the crash site.