Police were called to Dudley Town Hall, off St James's Road, at around 9.10pm on Friday after reports of an assault during a performance by comedian Jimeoin.
Two men were asked to leave the performance, before assaulting a security guard, West Midlands Police say.
A window was also smashed during the incident.
Jimeoin was performing at Dudley Town Hall as part of his Ramble On! tour.
West Midlands Police are now investigating the incident and are trying to trace the two men involved.
One audience member said: "Towards the end of the second part of his set, a fist fight broke out in the front quarter of the audience. It was sometime after 9pm.
"There was a fist fight, it was a big disturbance while the show was going on – Jimeoin had to stop and was just observing what was going on. The security staff got involved.
"We left at that point but we did see a police car with lights flashing heading in the town hall's direction."
A spokesman for West Midlands Police said: "Police were called to Dudley Town Hall at around 9.10pm on Friday night to reports of an assault.
"A security guard was assaulted by two men after they were asked to leave a performance due to their behaviour. A window was also smashed.
"Enquiries are on-going to trace the two men and anyone with any information has been asked to contact police."
Anyone with information can call West Midlands Police on 101, quoting incident number 20DY/246959Z/19.
Alternatively, contact Crimestoppers anonymously on 0800 555111 or at crimestoppers-uk.org