More than 1,000 Russians - including Olympic medallists - benefited from a state-sponsored doping programme between 2011 and 2015, a report claims.
At least 30 sports, including football, covered up samples, the report says.
"It was a cover-up that evolved from uncontrolled chaos to an institutionalised and disciplined medal-winning conspiracy," said the report's author, Richard McLaren.
Lawyer McLaren said London 2012 was "corrupted on an unprecedented scale".
The report also implicates medallists at the 2013 World Athletics Championships in Moscow, and the 2014 Winter Olympics in Sochi.
According to the report, salt and coffee were used to manipulate Russian samples.
The report added the system was refined over the course of the 2012 Olympics, 2013 Worlds and Winter Olympics to protect likely Russian medal winners.
Russia won 72 medals at the London Games, 21 of which were gold, and 33 medals at Sochi, 13 of which were gold.
McLaren's second report added depth and supporting evidence to the initial findings published in July - that Russia operated a state-sponsored doping programme.
That first report was met with denials from Russia and calls for more proof from the International Olympic Committee (IOC).
Writing in his latest report, McLaren says: "The desire to win medals superseded their collective moral and ethical compass and Olympic values of fair play."
He said international sports competitions had been "unknowingly hijacked by the Russians" and sports fans have been "deceived" for years.
"It is time that stops," he added.
In a statement, Russia's sports ministry said it would examine the report but insisted on "the absence of a state programme of support for doping sport". It said it would "continue to fight doping from a position of zero tolerance".
Russian MP Dmitry Svishchev, who is also the head of Russia's Curling Federation, was quoted by Ria Novosti news agency as saying: "This is what we expected. There's nothing new, only empty allegations against all of us. If you are Russian, you'll get accused of every single sin."
When asked for a reaction to those comments, McLaren said: "I would say read the report. Its findings are not challengeable. He is reacting in a vacuum because he has not read the report."
The new report also found:
- At the Sochi Games, two Russian female ice hockey players had male urine samples.
- A total of 15 Russian medal winners at London 2012 were implicated [10 medals have since been taken away].
- The samples of 12 medal-winning athletes at Sochi 2014 had evidence of tampering.
- Six winners of 21 Paralympic medals at Sochi had their samples tampered with.
- Emails were found asking for instructions from the Russian Ministry of Sport on what to do with a positive sample - save or quarantine?
- Spreadsheets were found containing lists of athletes whose samples had been saved.
- A clean urine bank was kept in Moscow.
- A cocktail of drugs - known as the "Duchess" - with a very short detection window was developed to assist athletes in evading doping.
- Salt and instant coffee granules were added to clean urine samples to match the appearance of the positive samples.
- Three samples at Sochi had salt readings that were physiologically impossible.
Investigators have published a searchable database of all the non-confidential evidence they have gathered here.
The full report can be read here.
How urine sample swapping worked
The first McLaren report explained how disappearing positive drug tests were secreted through "mouse holes" drilled by spies.
That was based on information received from Dr Grigory Rodchenkov, a director of the anti-doping laboratory at Sochi 2014.
He had said the Russian secret service developed ways of opening sample bottles and replacing their contents without intervention being detected.
The new report claims to have compiled clear details on exactly how the sample bottles in Sochi were tampered with.
Investigators used a tool which matched the description of one used by the FSB (Russian Federal Security Service), which leaves tiny marks and scratches when the inside of a cap is opened.
An expert was given 13 bottles, one of which had not been tampered with, which he immediately spotted.
In cases of alleged sample swapping, investigators found there were scratches and marks on the inside of the cap, along with DNA inconsistencies.
BBC sports editor Dan Roan
Once again the gory details of Russian state-sponsored cheating have been laid bare by Professor Richard McLaren.
The difference now is those claims have been backed up with concrete evidence.
Some of the details really do defy belief, and the fact the Russian government is so strongly implicated will inevitably lead to calls for Russian athletes to be banned from the 2018 Winter Olympics, and perhaps even for the 2018 football World Cup to be taken away from the country.
Reaction - 'hugely significant'
The IOC said the report showed "there was a fundamental attack on the integrity of the Olympic Games and on sport in general".
It said it would re-analyse all 254 urine samples collected from Russian athletes at Sochi 2014.
UK Anti-Doping chief executive Nicole Sapstead said the report was "hugely significant for sport and those who fight to keep it clean".
She added: "Everyone engaged in sport needs to ensure that the right processes, sanctions and safeguards are in place to protect everyone's right to clean, fair and honest sport."
She also called for more funding to support investigations.
Travis Tygart, chief executive of the United States Anti-Doping Agency said the Russian Olympic Committee should be suspended, and no sporting events should be held in the country until "all the individuals who participated in the corruption are held accountable".
The International Paralympic Committee (IPC) described the report's findings as "unprecedented and astonishing", adding: "They strike right at the heart of the integrity and ethics of sport."
The International Association of Athletics Federations (IAAF), the body that governs world athletics, said: "It is time that this manipulation stops." It said it will take further action once it is able to examine the latest report.
British marathon world record holder Paula Radcliffe said Russia had committed a "huge fraud". She added: "We need to know this cannot happen ever again."
Katherine Grainger, Britain's most decorated female Olympian, told BBC Radio 5 live: "This is a reminder that, along with all those high points in sport, there is a very dark side. It's depressing and it's slightly soul-destroying that it's on this scale."
Paralympic table tennis champion Will Bayley said: "I do have compassion for the athletes. Because if they were forced into it, and they are never going to be able to compete in the sport that they love, then that's really sad."
UK sports minister Tracey Crouch said: "The sheer scale of what has been uncovered underlines just how much more needs to be done.
"We will continue to assist on this front, including in Russia, where UK Anti-Doping is assisting Wada by managing a testing programme that we hope will lead to Russia becoming compliant with the Wada."
What is the reaction in Russia?
Stanislav Pozdnyakov, vice-president of the Russian Olympic Committee, told state news agency R-Sport the report contains "nothing new".
He said Russian athletes "should train calmly" for the 2018 Winter Olympics in Pyeongchang, South Korea.
Igor Lebedev, deputy speaker of the Russian parliament and a member of the executive committee of the Russian Football Federation, said: "This is yet another torrent of lies, disinformation, rumours and fables."
Natalia Gart, president of the Russian Luge Federation, said: "Where are the facts? You can say this is nothing but rubbish... I am convinced that all of our athletes are clean and the silver medals that we won at Sochi are well deserved."
What is Russia doing about doping?
The Russian Investigations Committee - the country's main anti-corruption body - continues to investigate criminal cases that have been launched.
The committee says 60 athletes have so far been questioned.
Senior officials from Russia's sports ministry, its anti-doping agency and the Russian Athletics Federation are also said to have been questioned.
On Wednesday, Russia's anti-doping agency (Rusada) appointed former double Olympic pole vault champion Yelena Isinbayeva to chair its new board.
The move was questioned by the World Anti-Doping Agency (Wada), which said Rusada broke an agreement it would be consulted before any appointment was made.
Isinbayeva, 34, was strongly critical of Wada's recommendation that all Russian athletes be banned from Rio 2016.
McLaren was asked whether Russians athletes could be trusted in the future.
He said: "I think the answer to that is yes but they need to reform themselves. I've spoken with many Russian officials since July and they are putting together a very comprehensive programme which, if implemented properly, will make a major difference."
What could happen next?
Wada says it will now pass evidence on Russian athletes' doping to the relevant international sporting federations and governing bodies.
In a news conference on Thursday, IOC president Thomas Bach said the McLaren report's findings would be taken up by two further commissions.
Only once those commissions had made their recommendations could the IOC decide what steps to take, he said.
"As soon as we have the report it will be handed over to the two commissions, who have already undertaken preparatory work," Bach said.
"But if you ask me for my private opinion then personally if you have an athlete being part of such a manipulation system, clearly I would not like to see this person compete again."
More on the IOC's two commissions
- The IOC says its 'Inquiry Commission', chaired by former president of Switzerland Samuel Schmid, will address the "institutional conspiracy across summer and winter sports athletes" with particular regard to Sochi 2014.
- Its 'Disciplinary Commission', chaired by IOC member Denis Oswald, will address "doping and manipulation of samples concerning the Russian athletes who participated at Sochi 2014".
What has already been done?
In May, McLaren was tasked by Wada with investigating allegations of doping in Russia.
He published the first part of his report - stating Russia operated a state-sponsored doping programme from 2011 - in July.
As a result, Wada recommended all Russian athletes be banned from competing from the Rio 2016 Olympics and Paralympics.
But the IOC chose not to impose a blanket ban, instead leaving decisions on whether Russians could compete to individual sporting federations.
Russia eventually took 271 athletes from an original entry list of 389 competitors to August's Olympic Games in Rio.
However, the IPC chose to ban the nation entirely from the Paralympics in September.
Last week, the IAAF decided to extend Russia's ban from international competitions.