Rumours of her departure have been circulating over the past month, and O'Donoghue today confirmed that she would leave the company, and has no new job lined up.
"Hat Trick has been a major part of my life and I have loved it but now it is time for something different. What that will be I have no idea - which is something of a novelty I intend to enjoy," said O'Donoghue, who will leave at the end of January.
O'Donoghue set up the company in 1986 with Jimmy Mulville, the other joint managing director, and went on to create a string of hits such as Have I Got News For You and The Kumars At No.42.
Her departure has sparked speculation that the BBC may come after her to run BBC3, following Stuart Murphy's departure to RDF last week.