The Brexiteer stated he wouldn't be surprised if there were "shenanigans" in the Lords and that any attempts to frustrate proceedings would be wrong.
Speaking on Talk Radio, the former Conservative leader underlined that many peers in the Lords were Lib Dems and he suspected amendments would be sent back to the House of Commons.
Put to him that there were "many, many" peers who were adamant that Britain should stay in the EU, Mr Duncan Smith said: "Yes, that's correct there are. Of course the difference in the House of Lords is that the Government doesn't have a majority in there.
Iain Duncan Smith has warned the House of Lords against delay on the Article 50 bill
Make your point but don't frustrate the will of the British people
Iain Duncan Smith
"In fact, quite bizarrely, the Liberal Democrats who crashed to defeat in the last election having, I think, only nine MPs now have over 100 peers in the House of Lords and they of course are determined to have that second referendum.
"So there may yet be shenanigans in the Lords, I'm sure there will be. It's their right to do what they like on this one but I think you'll see, in essence, the same kind of amendments repeated in the House of Lords.
"I suspect we will have some of those sent back to the House of Commons for us to say yes or no to, which we all of course want to say no."
But the Tory MP for Chingford and Woodford Green warned against lengthy consultation and suggested it wouldn't sit kindly with the British public.
He said: "I would have a simple word for them, which is by all means debate it and by all means make your point but don't frustrate the will of the British people. This is about triggering Article 50 nothing more, nothing less.
'We can't leave unless we trigger Article 50, we can't even start the negotiations unless we trigger Article 50 so any attempt to delay or to amend it to the point that makes it impossible for the Government to do anything would, of course, be a deliberate slap in the face to the British people."
Brexit aftershocks: Who's next to leave the EU? Wed, September 14, 2016
Britain has voted to leave the EU. So who's next? We look at which European countries want to hold their own EU referendum.
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Frexit, Nexit or Auxit? Who will be next to leave the EU
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Mr Davis stressed the Government fought off a series of attempts to amend the European Union (Notification of Withdrawal) Bill before it passed through the Commons in a "historic vote" by MPs on Wednesday.
It will now need to be approved by peers before Theresa May can begin exit talks under Article 50 of the EU treaty, which she has promised by April.
The MP for Haltemprice and Howden said: "I expect it to do its job and to do its patriotic duty and actually give us the right to go on and negotiate that new relationship (with the EU)."
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