People in Wales will be presumed to have given consent for organ donations unless they opt out after a vote in favour of the law.
The current system, which operates across the UK, relies on people signing up to a voluntary scheme and carrying a donor card.
But Welsh ministers keen to drive up low transplant rates say the new scheme - set to come into force in 2015 - will save countless lives.
The new bill for Wales to adopt a system of presumed content passed its final stage in the Welsh Assembly, despite objections from religious groups on moral grounds as well as concerns about it adding to the distress of bereaved families.
Assembly Members voted in favour of the bill by 43 votes to eight, with two abstentions.
The Kidney Wales Foundation welcomed the vote, saying it "gives new hope for all those waiting for a transplant in Wales and will gladden the hearts of those in the UK who see this as a sign that other parts of the UK may follow this vote".
The organisation said one person dies every week in Wales - and three die every day in the UK - while waiting for an organ transplant.
Ministers insist the scheme will be implemented sensitively - saying they will launch a major publicity drive so people are fully informed about which choice to make.
The British Medical Association's spokesman in Wales said: "A few years ago, Wales was ready to lead the UK on banning smoking in public places, but we didn't have the necessary legal powers.
"This time we are delighted that our National Assembly has shown the rest of the UK the way forward and fully support its implementation."
The Welsh government said it hoped the new law would increase donors by a quarter. It will mean people would have to choose not to donate their organs and would apply to over-18s who died in Wales if they had lived in the country for more than a year.
Organs made available under the scheme could be used anywhere in the UK.
Despite five years in the making, the issue was still hotly contested for five hours before the vote with AMs from the Assembly's four parties mulling over more than 70 amendments.
Clwyd West AM Darren Millar voiced his objections saying: "I'm opposed in principle to a system where organ transplantation becomes a passive act, and consent for it is presumed, or as the Bill puts it deemed, by the state."
But his Tory colleague Angela Burns said she was still undecided right up until voting time.
Plaid Cymru's health spokeswoman Elin Jones said the Bill was an "important piece of legislation", but added it needed to be supported by an awareness campaign.
Lib Dem leader Kirsty Williams acknowledged the issue was an "incredibly emotive" one, but said the Bill would save lives.
Celebrity doctor and Embarrassing Bodies TV presenter Christian Jesser tweeted: "Having an opt out system for organ donation has not removed any rights from you. You can still opt out. That's the point!"
However, those views were not shared by campaign group Patient Concern, whose spokeswoman Joyce Robbins said: "This legislation will result in human bodies being treated like clapped-out cars. You strip them of parts for re-use, unless the owner prefers to scrap the whole vehicle."
The Christian Medical Fellowship branded the presumed consent model "unethical". Its chief executive Dr Peter Saunders said: "It should be encouraged as a gift, but this system lays the framework for the taking of organs as a right. That is a very dangerous precedent indeed."
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