Data from the Office for National Statistics (ONS) showed 484,510 residents were not contributing and fell under the classification on March 15 and 22.
An "economically inactive" person is aged 16 or over, did not have a job in that time period, could not start work in the next two weeks – or had not looked for work in the month before.
Louise Murphy, economist at the Resolution Foundation, said: "Levels of inactivity vary significantly across the UK, and tend to be highest in places where the population is older, and where long-term illness is widespread, such as deprived, ex-industrial areas.
"Economic inactivity is also concentrated in low-income households. One-in-three adults in the poorest tenth of households have a disability, compared to fewer than one-in-ten adults among the richest families.
"The right approach to boosting workforce participation should therefore focus both on tackling place-based inequalities, as well as raising living standards for the poorest families."
In Dudley, 107,985 residents came under the classification, or 41.1 per cent of over 16s in the area. In Wolverhampton, it was 85,455 or 41 per cent. In Sandwell, it was 110,830 or 41.7 per cent. In Walsall, it was 94,605 or 42.4 per cent.
In Stafford, it was 45,230 or 39.8 per cent. And for South Staffordshire, it was 40,405 or 43.3 per cent.
Amanda Walters, director of the Safe Sick Pay campaign, highlighted rising numbers of people not working due to long-term sickness or disability.
"Help from the Government to support these people back into work will be very welcome, but people fear what happens if they get ill again," she said.
"The 'back to work' budget had the right focus, but it was an own goal from the Chancellor not to make sick pay available for everyone from the first day of illness."
Chancellor Jeremy Hunt said he will deliver growth with his 'back to work' budget by "removing obstacles that stop businesses investing, tackling labour shortages that stop them recruiting, and by breaking down barriers that stop people working".
Mr Hunt added that he will encourage the long-term sick and disabled into work, including announcing the Universal Support programme – a voluntary employment scheme for disabled people where the Government will spend up to £4,000 per person to help them find appropriate jobs.
Schemes to encourage young carers, older people nearing retirement and parents – including 30 hours of free weekly childcare for all under-5s – to work were also introduced.
"Our plan is working – inflation falling, debt down and a growing economy," Mr Hunt added. "Britain is on a lasting path to growth with a revolution in childcare support, the biggest ever employment package and the best investment incentives in Europe."