Crews were called to Shirley High Street in the early hours after the blaze broke out at the building used by the Paddy Power betting shop.
Traders with shops in Shirley High Street were standing in the rain as they waited for the cordons to be lifted.
Portsmouth firefighters battling large blaze on Hampshire high street
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The high street is closed in both directions as around 30 firefighters battle the blaze this morning (November 21).
Pictures from the scene appear to show that the fire is affecting the Paddy Power bookmaker in Shirley.
Hampshire Fire and Rescue tweeted: We are currently dealing with a large fire in #Shirley High Street.
As well as the eight fire engines at the scene there are also two aerial ladder platforms in Shirley as firefighters battle the blaze.
The Bluestar 4, 7, 17 and 18 buses will not be stopping at Shirley Precinct and Church Street as a result of the fire – with passengers advised that the closest bus stop is Shirley Police Station.