He will leave after more than three years in the role at the inspectorate, which is in charge of monitoring national policing effectiveness and efficiency.
Sir Denis spent five years as an Inspector of Constabulary before being promoted to Chief Inspector in 2009.
Home Secretary Theresa May said: ‘I would like to thank Sir Denis O’Connor for his dedication and commitment to HMIC, both as inspector and chief inspector, during the past eight years.
‘His expertise and knowledge have been invaluable in enabling the inspectorate to continue to deliver an efficient and independent inspection programme during many challenges and changes in the policing landscape.
‘I would also like to commend him for his dedicated, long-standing and exemplary service to wider policing in England and Wales.’
Before joining the inspectorate, Sir Denis was Chief Constable of Surrey Police between 2000 and 2004. A new appointment to the post will be made later this year.