The force said they were called just after 8.30pm on Sunday to the incident on Dulwich Road in Kingstanding.
One house has been destroyed and several others have been significantly damaged as well as nearby cars.
Casualties have been reported but the number and severity of their injuries is unknown at this time, police said.
The force thanked those who had “helped shocked and injured neighbours”.
Footage on social media shows flames, damage and debris from a terraced red brick house.
Aerial shots shared on Twitter also show flames billowing into the sky.
Evacuations are taking place and people have been urged to avoid the area, with Dulwich Road and surrounding roads closed.
Emergency services said the cause of the fire is not yet known.
West Midlands Fire Service (WMFS) said West Midlands Police, West Midlands Ambulance Service, Cadent Gas and the National Grid are all working to manage the incident.
Six fire crews, three ambulances, five paramedic officers and a National Inter-Agency Liaison officer are among the resources that have been sent to the scene.
West Midlands Police tweeted: “Thank you for all you kind words. Our thoughts are with everyone affected by this.
“Emergency workers form all services and the energy companies are working really hard in very difficult circumstances.
“Thanks to people who have helped shocked and injured neighbours.”
West Midlands Ambulance Service tweeted: “We have sent three ambulances, five paramedic officers, the MERIT trauma doctor and critical care paramedic, @wmcareteam @WMASHART and a NILO to the scene.”
WMFS tweeted: “Six fire crews are in attendance at this incident involving an explosion on Dulwich Road, Kingstanding. Please avoid the area at this time.”
In a statement on its website, WMFS added: “At 20.38 fire crews responded to multiple reports of an explosion on Dulwich Lane, Kingstanding.
“The explosion, the cause of which is unknown at this time, has destroyed one property and caused damage to other properties and vehicles nearby.
“The number of casualties or injuries is not confirmed at this time,” it said.
“West Midlands Police are managing evacuations in the area and we urge those local to the incident to follow the instructions of emergency service officers at the scene.”