Data from NHS Digital – rounded to the nearest five – revealed roughly 2,950 medical and administration workers left their posts in 2021-2022 in the area.
And it represented record highs in Wolverhampton, Sandwell, Walsall and Staffordshire with Dudley the only health trust to see a slight decline.
It comes as the number of resignations soared in England with union chiefs blaming poor pay and a lack of mental and physical support for staff.
Pat Cullen, general secretary and chief executive of the Royal College of Nursing, said: "Years of underinvestment – including a decade of real-terms pay cuts – means record numbers of staff are leaving the NHS.
"Staff are leaving, realising they can get similar or better pay in supermarkets and retail without the stress of the job, and poor pay is creating severe staff shortages and making patients unsafe.
"Nurses, patients, and the public deserve better than a government that won’t listen."
The resignation data does not necessarily mean the staff member has left the NHS altogether – with the figures also including any promotions or relocations, NHS Digital said.
At the Royal Wolverhampton NHS Trust, which runs New Cross Hospital, the figure was at 805 in 2021-2022 compared to the 635 in 2019-2020, before the pandemic.
At the Walsall Healthcare NHS Trust, which runs Walsall Manor Hospital, it was 455 compared to 375. At the Sandwell and West Birmingham NHS Trust, which runs Sandwell General Hospital and Birmingham City Hospital, it was 685 compared to 575. At the University Hospitals of North Midlands NHS Trust, which runs Stafford's County Hospital and the Royal Stoke University Hospital, it was 750 compared to 555.
Each of the figures were record highs except for the Dudley Group NHS Foundation Trust, which runs Russells Hall Hospital, which had 255 staff leaving their posts compared to 295 before the pandemic.
Meanwhile, the number of hospital and community health service doctors across the country resigning also reached record levels during the pandemic, rising from 8,225 in 2019-20 to 9,305 last year.
Dr Latifa Patel, chair of the representative body and workforce lead at the British Medical Association, said the rise in resignations is unsurprising due to the difficulty in finding a "healthy work-life balance".
Dr Patel added: "Fixing the workforce crisis isn’t just about recruiting more people, but also about retaining the staff already in the NHS. This starts with the Government paying them fairly, and publishing its NHS workforce plan as soon as possible."
The Royal College of Midwifery also said falling pay is a primary issue for many who leave the profession.
An RCM spokesperson said: "Midwives have seen over a decade of pay stagnation, and feel undervalued and burnt out.
"Now is the time for the Government to act – to offer midwives a decent pay deal and start tackling the serious problems facing our maternity services."
The Department for Health and Social Care said it has given one million NHS workers a pay rise of at least £1,400 this year, as well as a three per cent cost-of-living pay increase last year.
A comprehensive workforce strategy to help recruit and retain more staff will be published this year, a spokesperson added.
They said: "There are already record numbers of staff working in the NHS, with 4,700 more doctors and over 10,500 more nurses compared to last year, and we are committed to 50,000 more nurses in the NHS by the end of this parliament."