Officers believe the victims and suspects are known to each other.
Easton Way is closed between the junction with Stapleton Road and Pennywell Road.
There is also no access to Easton Way from Old Market.
Police are seeking witnesses from the Stapleton Road and Rawnsley Park area between 04:15 and 05:00.
Neighbourhood Policing Ch Insp Scott Hill said: “This is a significant incident and I am conscious there have been a number of similar incidents of this nature over the past few months.
“I also understand there is a great deal of concern among the community around knife crime.
“We remain dedicated to reducing serious violence and knife crime, especially among young people.
“Earlier this year, we launched a proactive operation targeting serious violence and knife crime and we are working closely with partners to identify and tackle the root causes.”
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