West Midlands Mayor Andy Street said the series of incidents in the Hurst Street area of the city centre appeared to be related but the motivation for them was not yet understood. Five others received "relatively minor" injuries.
Three of the five taken to the major trauma centre had critical injuries and one man was pronounced dead shortly after arrival, WMAS said.
"We immediately attended, along with colleagues from the ambulance service", their statement reads.
West Midlands Police declared a major incident after officers were called to reports of a knife attack in the early hours of Sunday, with further stabbings then being reported.
They set up a cordon at the junction of Hurst Street and Bromsgrove Street - an area which has always been at the heart of the LGBT+ neighborhood with a number of LGBT+ bars.More news: Deshaun Watson signing monster extension with Houston
Passers-by fled the violence, as police and other emergency services arrived quickly and cordoned off the area. Forensic specialists were at the scene by mid-morning.
Several yellow police evidence markers could also be seen on the ground, some near to broken glass.
Police said the response would be ongoing "for some time" and urged people to stay away from the area.
'At this stage it would not be appropriate to speculate on the causes of the incident'.
The streets in the area had already been closed to traffic due to Coronavirus restrictions.More news: Trump calls for resignation of reporter for `fake news`
Foreign Secretary Dominic Raab said it was "a very serious incident".
The West Midlands Police and Crime Commissioner David Jamieson, said: "Last night's events are truly bad and have shocked the people of Birmingham, the West Midlands and the country".
The West Midlands PCC David Jamieson says his thoughts are with those who have been affected.
"I have been saying for some time, in the context of COVID-19 that a lot of the feelings people have and not being able to get out and combine that with people who are now unsure about their future and their jobs, it was nearly inevitable that we would see a growth in violence".
But she said there remained a real issue with social exclusion among younger people, including "county lines" drug dealing.More news: Call of Duty: Black Ops Cold War Multiplayer Footage Leaks