Iain Duncan Smith has been accused of "striking fear into the hearts" of the sick as he unveiled plans for more welfare reforms.
The Work and Pensions Secretary declared that work is "good for your health" and can help people recover from illness.
He signalled that, in future, benefits assessments will check what tasks people could do - rather than putting them in "binary" categories of either fit for employment, or signed off entirely.
However, Labour leadership candidate Andy Burnham is set to attack Mr Duncan Smith's plans as an effort to "cover his own failures".
Mr Duncan Smith insisted too many people with "common" mental illnesses are reliant on state payouts, when they could be earning a wage.
"There is one area on which I believe we haven't focused on enough - how work is good for your health," he said.
"Work can help keep people healthy as well as help promote recovery if someone falls ill.
"So, it is right that we look at how the system supports people who are sick and helps them into work.
"Let me be clear: a decent society should always recognise that some people are unable to work as a result of physical or mental ill health - or both.
"It is right that we protect these most vulnerable people in our society. That support is there.
"For, despite the scaremongering, it is worth reflecting on the fact that we in this country spend more on sick and disabled people than the OECD (Organisation for Economic Co-operation and Development) average."
In the speech - which media were not allowed to attend - Mr Duncan Smith said: "We know there remains a gap between the employment rate of disabled and non-disabled people.
"We want to ensure everyone has the opportunity to transform their lives for the better by getting into work.
"That's why, as part of our one nation approach, we have committed to halving this gap."
The work capability assessment system that determines if someone will receive the employment and support allowance (ESA) has been dogged by controversy since its introduction under Labour.
Mr Duncan Smith said ESA was supposed to reduce the number of people on incapacity benefits by one million, but since 2010 there has been a fall of just 90,000 - and plans to reform the process will now be drawn up.
Nearly one in four jobseeker's allowance claimants have a common mental health condition and need more support to find, and stay, in employment, he added.
Mr Duncan Smith said: "ESA may have been designed with the right intentions, but at its heart lay a fundamental flaw. It is a system that decides that you are either capable of work or you are not.
"Two absolutes equating to one perverse incentive - a person has to be incapable of all work or available for all work.
"This needs to change - things are rarely that simplistic.
"We need to look at the system and in particular the assessment we use for ESA - and I want to look at changing it so that it comes into line with the positive functioning of Universal Credit, and as such is better geared towards helping to get people prepared for and into what work they may be capable of, rather than parking them beyond work.
"We need a system focused on what a claimant can do and the support they'll need - and not just on what they can't do."
He added: "Nearly 11 million adults in the UK have a common mental health condition and people are much more likely to fall out of work if they do.
"We also know that being out of work for four weeks or more can actually affect people's mental health, even if the original reason for ill health was a physical one."
At a campaign rally in London later, shadow health secretary Mr Burnham will say: "It's clear that Iain Duncan Smith is now preparing a new attack on disabled people to cover for his own failures on social security.
"Talk of cutting support for people who are simply not able to work will strike fear into the hearts of many vulnerable people.
"The cruel and crude approach of the Tories has already driven many people to despair and this new drive will cause even more anxiety."