Officers were called to North Terrace just after 2am on Monday to find a 25-year-old Victorian man lying on the road with multiple stab wounds to his chest. He died shortly afterwards.
Detectives arrested the 17-year-old Meadows Heights boy at Adelaide Airport as he tried to return to Victoria.
The boy was charged with murder, aggravated affray and travelling under a false name.
Another three Victorians, an 18-year-old man, a 21-year-old man and a 16-year-old boy, were also arrested at the airport and charged with offences including aggravated affray.
The four were refused bail to appear at the Adelaide Magistrates Court on Tuesday.
South Australian Assistant Commissioner John Venditto said police believed the fatal altercation was linked to Operation Meld, a crackdown targeting youth gangs.
"The theory at the moment is that this is an incident between two groups that know each other," he told reporters on Monday.
"The threat to the public is there because they've got bladed weapons and other weapons and react with spontaneous acts of violence."
Another 13 people were arrested on Monday for a range of offences, including weapons and assault charges.
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