About 40 firefighters attended the blaze at a community resource centre in Blantyre.
The Scottish Fire and Rescue Service was first alerted to the incident in Calder Street at 1.48am on Monday.
Eight fire engines including two aerial appliances and a forward control unit were sent to the scene.
Firefighters were working externally to tackle the flames using powerful water jets.
A spokeswoman for the SFRS said: “There are no reported casualties at this present time.”