The interim chief executive at NGH will leave the hospital in June.
Christine Allen took over the top job on a stand-in basis from Dr Gerry McSorley at the end of March.
But she will leave in June, by which time the hospital hopes to have recruited a new boss.
An NGH spokesman said: “Christine Allen, currently interim chief executive at Northampton General Hospital, has been appointed as chief executive for James Paget University Hospitals NHS Foundation Trust in Norfolk, and will leave Northampton at the end of June.
“Interviews for her replacement at NGH are planned, and Dr Sonia Swart our current medical director and deputy chief executive will provide continuity.”
Mrs Allen’s main role, chief operating officer, will be filled on an interim basis by Clive Walsh of Leeds Teaching Hospitals. He currently holds an equivalent role at that trust, also as an interim.
The spokesman said: “Clive has significant experience in operational management within the acute healthcare sector, having worked in a range of hospitals. Clive joins us on 29 April and we look forward to working with him.”