But the man dubbed "The Butcher of Bosnia" was not present in court to hear the final verdict, having been dragged out of the courtroom after loudly accusing the judges of "lying". And his son and lawyers told reporters he planned to appeal.
Judges at the International Criminal Tribunal for the former Yugoslavia (ICTY) found Mladic guilty on 10 counts including genocide, war crimes and crimes against humanity such as murder and deportation. He was however acquitted of one charge of genocide in certain municipalities.
About 100,000 people were killed and 2.2 million displaced in the 1992-1995 war when ethnic rivalries tore Yugoslavia apart.
Judges said "ruthless" Bosnian Serb forces under Mladic's command carried out "mass executions" and showed "little or no respect for human life or dignity."
"For having committed these crimes, the chamber sentences Mr Ratko Mladic to life imprisonment," presiding judge Alphons Orie said as applause broke out in the public gallery.
He added the crimes were "amongst the most heinous known to humankind".
A smiling Mladic, 74, who once left a trail of fear across Bosnia, gave a thumbs-up as he entered the courtroom in The Hague dressed in a grey suit with a red tie.
Bosnian Serb army commander Ratko Mladic addresses his troops in the eastern Bosnian town of Vlasenica in December 1995. Source: AP
But in dramatic scenes he was later ordered to be removed, after accusing the judges of lying, when they refused to adjourn the hearing because of his high blood pressure.
"They are lying, you are lying. I don't feel good," he shouted, as two UN security guards hustled him into a nearby room to watch the rest of the verdict.
'Accept the truth'
Bosnian Muslim leader Bakir Izetbegovic on Wednesday urged ethnic Serbs to "accept the truth" after Mladic's sentencing.
"Accepting of the truth is the only path, the only way, that the future in this country will become better that the past," Mr Izetbegovic told a press conference in Sarajevo.
"No people, neither Serbian, should call Ratko Mladic a hero, make songs about him, glorify crimes."
Mr Izetbegovic said he was convinced Serbs did not identify themselves with Mladic and his crimes, which the leader said should be "put on Ratko Mladic and removed from the Serbian people's shoulders".
"It is of crucial importance for future in Bosnia-Hercegovina, notably for inter-ethnic ties, to remove such burden from people and place it on individuals.
"The past is behind us, it is worth referring to only as much as it can influence a better future."
Mr Izetbegovic, the Muslim member of Bosnia's joint presidency, is the son of Bosnian Muslim wartime leader Alija Izetegbovic who died in 2003.
Tears in court
Wednesday's verdict was long awaited by tens of thousands of victims across the bitterly-divided region.
Dozens gathered early outside the courtroom, many clutching photos of loved ones who died or are among the 7,000 still missing.
It was an emotional day for victims, some of whom sobbed in the public gallery as the judges recalled brutal scenes of rape and murder. In Srebrenica there were tears of joy.
"Mladic will die in The Hague! I'm so happy that justice has been done!" said Nedziba Salihovic, who lost her husband, father and son in the 1995 Srebrenica massacre.
The court found Mladic guilty of genocide in that northeastern town, where troops under his command slaughtered almost 8,000 Muslim men and boys.
The killings, in which the victims were marched away, shot in the back and dumped in mass graves, was one of the darkest episodes in the conflict, and has been called the worst atrocity on European soil since World War II.
Bosnian Muslim leader Bakir Izetbegovic on Wednesday urged ethnic Serbs to "accept the truth" after Mladic's sentencing. Source: Getty Images
Mladic "intended to eliminate the Bosnian Muslims in Srebrenica by killing men and boys and forcibly removing the women, young children and some elderly men," Orie said.
Munira Subasic, president of the Mothers of Srebrenica association, said she was "partially satisfied" with the verdict.
"It's more than for (Radovan) Karadzic. But they didn't find him guilty for the accusation of genocide in some villages," she said.
Karadzic was sentenced to 40 years in March 2016 for similar charges, including the Srebrenica genocide. He is appealing the sentence.
Edin Halilovic, 18, whose grandfather died in Srebrenica, said it had been important to attend the hearing. "My generation, and future generations, must never forget what happened to our families."
A victim's relative reacts as she watches a live TV broadcast from the International Criminal Tribunal for the former Yugoslavia (ICTY). Source: Getty Images
Milestone for justice
Chief prosecutor Serge Brammertz said the verdict marked as a "milestone" for the court and for international justice.
Mladic's was the last genocide trial before the tribunal which will close its doors on December 31, having indicted 161 people since it was set up in 1993.
Praising the victims as the only "true heroes," Brammertz insisted it was not a verdict against the Serbian people.
"Mladic's guilt is his and is alone," he said.
Mladic was also found guilty of having "personally directed" a 44-month campaign of sniping and shelling in the Bosnian capital Sarajevo, in which 10,000 people died.
And he was convicted for the hostage-taking of more than 200 NATO military personnel.
But defence lawyers have slammed the trial as "political".
"This sentence is unjust and contrary to the facts and we will fight it on appeal to prove that this judgement is wrong," his son Darko Mladic told reporters.
"Today justice has been replaced by war propaganda," he added.
His lawyers insist Mladic senior is in ill-health, and urged the hearing to be adjourned, claiming he was in "hypertensive crisis" due to high blood pressure.
International reaction was swift. Serbian President Aleksandar Vucic urged fellow Serbs to look to the future rather "than suffocating in tears of the past".
The European Union urged Balkan countries to "honour the victims" by working towards reconciliation, while the UN said it was a "momentous victory for justice".
