In his role, Middleton is responsible for Trinity's entire print arsenal, incorporating facilities in Birmingham, Blantyre, Cardonald, Cardiff, Liverpool, Newcastle, Oldham, Teeside and Watford.
Middleton is moving to an as yet undisclosed non-competing company, although PrintWeek understands he will remain in print.
He said: "I will miss newspapers a lot. There is a really good team at Trinity and it’s a great time to be in newspaper printing."
Middleton joined Trinity Mirror in March 2004 from The Stationery Office (TSO), although he had spent 10 years at fellow newspaper printer Westferry prior to that.
Chief executive Sly Bailey said: "We are grateful to Rupert for his leadership in turning TMP into the pre-eminent newspaper printer in the UK. We are sad to lose him and wish him well. We have a strong team at TMP, who will continue to give outstanding service to their customers and will take the business forward."
A replacement has not been selected; however Trinity has started a search for one.