Hundreds of people gathered outside the venue hosting the biennial Land Forces International Land Defence Exposition with many chanting pro-Palestine slogans through loud speakers and waving Palestine flags, video showed.
Riot squad officers and mounted police were seen trying to contain the protest within barricades. Australian media reported it was the largest police operation in Melbourne since 2000 when Australia's second-largest city hosted the World Economic Forum.
Victoria state police did not immediately respond to a request seeking comment.
Police detained protesters with handcuffs as dumpsters were pushed towards police lines, while some protesters yelled at delegates attending the conference, ABC News said.
Police have closed several major roads in the city and urged motorists to avoid parts of the city. One protester climbed on top of a truck that was stopped at traffic lights.
About 1,000 firms from 31 countries are expected to attend the event through Friday, which the organisers said was Australia's largest defence expo.
Prime Minister Anthony Albanese said people had the right to protest but had to do it in a peaceful manner.
"You don't say you're opposed to defence equipment by throwing things at police. They've got a job to do and our police officers should be respected at all times," Albanese told Channel Seven.