Job Centre staff will be stationed in GP surgeries and physiotherapy clinics in an effort to get sick patents off benefits and back to work.
The careers advisors will encourage jobless patients to return to the workforce and help them find suitable employment.
The NHS will work with the Government to trial the scheme from early next year, starting in areas with high levels of economic inactivity due to ill health.
It will then be rolled out nationwide if it is proven to boost wellbeing and tackle the nation's sick note culture.
Amanda Pritchard, chief executive of NHS England, said last night: 'By tackling a rise in health-related economic inactivity and by helping people stay in work or get back to work, the NHS can be a key driver for economic growth in England.'
One in ten people of working age - equivalent to 3.9million adults - now receive health-related benefits in England and Wales.
This is up 38 per cent from 2.8million people in just four years, according to the Institute for Fiscal Studies.
Over this period, real-terms spending on incapacity or disability handouts has increased by a third, from £36billion to £48billion and is expected to hit £63billion by 2028.
Backed by £45 million from the autumn Budget, the trial will see the NHS create 'Health and Growth Accelerators' in South Yorkshire, North East and North Cumbria, and West Yorkshire.
The three areas will look to boost people's health alongside tackling the conditions that most impact people's ability to work, including heart disease, diabetes, back pain and poor mental health.
Staff will increase efforts to prevent the diseases that lead to people dropping out of work by helping them manage their illnesses and supporting them to make lifestyle changes.
The accelerators, announced this week at the NHS England board meeting, will also test the use of phone apps and websites to support mental health therapy sessions and musculoskeletal pain.
Health secretary Wes Streeting has previously vowed to reform the health service so it is more effective at getting sick people back to work.
Speaking at an Institute for Public Policy Research event in September, he highlighted how a drop in productivity due to ill health 'has cost our economy £25 billion since 2018' and how 900,000 more people are off work than would have been on pre-pandemic trends.
'That's more people than Tesco, Sainsbury's and Asda employ put together,' Mr Streeting said.
'Fail to act and by the end of this parliament, 4.3 million people could be off work sick. Millions of people left behind, the welfare bill will balloon, and growth will be hampered.'
Alongside the accelerators, NHS England is working with the Office for National Statistics to assess the economic benefits of several health interventions including talking therapies, bariatric surgery, treatment for endometriosis, and the NHS Type 2 Diabetes Prevention Programme.
The analysis will cover the impact on waiting times, employment rates and earnings while feeding into work by the Office for Budget Responsibility and the government on labour market effects.
A pilot scheme in the North East and North Cumbria, led by the integrated care board and the Department for Work and Pensions, has already helped almost 2,000 people back to work through one-to-one support in County Durham and the Tees Valley.
Samantha Allen, chief executive at North East and North Cumbria Integrated Care Board, said 'Our GPs often see patients who want to be at work, but need practical, non-medical help as well as what a doctor can offer.
'Having a job, a steady income and feeling useful make a big difference to people's health – and so far almost one-third of patients seeing an advisor have successfully got back to working life.'
Professor Kamila Hawthorne, chair of the Royal College of GPs, said: 'We know that in general, working can be beneficial for our patients' health, so ensuring they get the support they need to get back to work, when it is safe for them to do so, is a good thing.
'However, it's important we don't push patients into work or back to work before they're ready, as this could have a detrimental impact on their health.'
Parth Patel, associate director at the IPPR, said: 'Most of those who are unwell would like to get back to work if they could be better supported to do so.
'This pilot brings together local health and employment services in a way recommended by our commission report, backed by evidence, to help raise health wellbeing and growth across the nation.'