The venue was packed for a performance of the Arthur Miller play Death of a Salesman.
The partial ceiling collapse happened above the circle and led to more than 1,000 people being evacuated from the cinema by the emergency services.
Ambassador Theatre Group said: “We are sorry to confirm that at 8pm this evening during a performance at the Piccadilly Theatre a section of plasterboard fell from the upper rear circle.
“The performance was immediately stopped and the theatre safely evacuated.
“Five members of the audience sustained minor injuries and were taken to local hospitals.”
ATG said it has now launched an investigation into the cause of the collapse.
The incident led to a call by Westminster Council for theatre owners to carry out thorough building checks.