Mass migration will make it "impossible to build a cohesive society", Theresa May will say.
Millions of people from poorer nations want to live in Britain but there is a limit to the amount of migrants the country can take, the Home Secretary will say. Mrs May has also announced that the Government will stop European Union nationals from making asylum claims in Britain.
In a speech at the Conservative Party conference in Manchester, she will say the "desire for a better life is perfectly understandable". She will add: "There are millions of people in poorer countries who would love to live in Britain, and there is a limit to the amount of immigration any country can and should take.
"While we must fulfil our moral duty to help people in desperate need, we must also have an immigration system that allows us to control who comes to our country.
"Because when immigration is too high, when the pace of change is too fast, it's impossible to build a cohesive society. It's difficult for schools and hospitals and core infrastructure like housing and transport to cope. And we know that for people in low-paid jobs, wages are forced down even further while some people are forced out of work altogether.
"But even if we could manage all the consequences of mass immigration, Britain does not need net migration in the hundreds of thousands every year."
Meanwhile, Boris Johnson will warn the Tory leadership to protect the lowest paid as it reforms welfare amid growing calls for Chancellor George Osborne to rethink cuts to tax credits.
Millions of working households are expected to be left out of pocket as tax credits are slashed ahead of planned rises in the minimum wage and further cuts to the personal allowance.
In his final speech to the conference as London mayor, Mr Johnson is expected to tell activists they must use the election of Jeremy Corbyn as Labour leader to truly seize the mantle of the party which helps all people succeed.
But David Cameron has defended the cuts, insisting they are part of an overall package that "help make work pay" and claiming that some families will be £2,400 better off under the reforms.
The Prime Minister told BBC 2's Newsnight: "This was a package put together which I think in the long term does help make work pay, but also crucially reduces the cost of welfare so we can keep taxes down and afford to fund our National Health Service and our schools."
The conference fringe has been dominated by discussion of who will succeed Mr Cameron as Tory leader, with Mr Johnson widely perceived as falling behind other rivals at the same time as the Chancellor cements his state as the firm favourite.
Speaking at the conference, the mayor is set to join Tory calls for a fresh look at tax credit changes. He will say: "We must ensure that as we reform welfare and we cut taxes that we protect the hardest working and lowest paid.
"Shops workers, cleaners, the people who get up in the small hours or work through the night because they have dreams for what their families can achieve - the people without whom the London economy would simply collapse.
"(These are) the people Labour is leaving behind and then there is an even more important requirement. If people are to feel bound in to this system then there must be hope and aspiration, and above all there must be opportunity and it is here that we Tories have a massive advantage.
"Because if Labour is once again becoming the party that pointlessly bashes the rich it is we who give everyone the tools to make their own lives and their own successes."
Mr Johnson will appear alongside Zac Goldsmith, the Conservative candidate to replace him in City Hall at May's mayoral elections.
Mr Johnson's planned remarks on welfare reform will follow a growing row both inside and outside Tory ranks on tax credit cuts, which have already cleared the Commons.
Mr Osborne has rebuffed critics of cuts to tax credits, insisting it was failure to control public spending that would be "economic cruelty" for working families.
He hit back after David Davis joined Tory demands for a rethink, warning that the squeeze could prove as damaging to the party as the poll tax was under Margaret Thatcher.
The independent Institute for Fiscal Studies has warned that 13 million families will lose an average of £240 a year when the cuts come into effect in April, while three million will lose £1,000 or more.
Health Secretary Jeremy Hunt sparked fresh controversy when he told a fringe meeting tax credit cuts are a "very important cultural signal" as Britain seeks to match the work ethic of Asian and American countries.