He has played a prominent part in the ongoing pro-EU demonstrations in Ukraine, frequently delivering rousing speeches to protesters in Kiev and across the country.
He was one of the most recognisable figures involved in the Orange Revolution of 2004-05, which overturned Viktor Yanukovych's election as president amid allegations of vote-rigging.
Shortly afterwards, Mr Lutsenko was appointed as interior minister.
Mr Yanukovych, however, went on to win the presidency in 2010, and later that year Mr Lutsenko was jailed on charges widely seen as politically motivated.
Mr Lutsenko is known for his blokeish sense of humour and sharp tongue.
His eloquence has frequently been deployed to good effect to rally opponents of President Yanukovych - as well as those of President Leonid Kuchma before him.
Yuriy Lutsenko's rise to prominence began with the Socialist Party in the early 1990s.
Later, he was a driving force behind protests against President Kuchma following the gruesome killing of independent journalist Heorhiy Gongadze in 2000.
After President Viktor Yushchenko came to power in 2005, Yuriy Lutsenko was appointed interior minister in Yuliya Tymoshenko's cabinet.
He made eradicating police corruption in Ukraine a key priority.
"I will either do it or my political career is over," he said at the time.
But as bickering intensified within the government, Yuriy Lutsenko grew increasingly critical of President Yushchenko, whom he accused of "betraying the ideals of the Orange Revolution".
He remained an ally of Yuliya Tymoshenko and later campaigned for her release following her controversial jailing on corruption charges in 2011.
Yuriy Lutsenko's tenure as interior minister was often marked by controversy.
An anti-graft campaigner, he was sacked by parliament in 2006 amid allegations of corruption - which, a court ruled, did not benefit him personally.
Mr Lutsenko said the move was instigated by his political opponents, and was re-appointed as interior minister a year later.
In 2008, Mr Lutsenko was accused of assaulting then Kiev mayor Leonid Chernovetsky, whom he accused of corruption.
Blunt language used against his opponents sometimes landed Mr Lutsenko in trouble, and in 2009 he lost a libel case filed by a pro-Yanukovych MP.
Also in 2009, Mr Lutsenko was detained at Frankfurt airport after an altercation with police while apparently drunk.
Shortly before Mr Yanukovych defeated Mrs Tymoshenko in a presidential election runoff in February 2010, Mr Lutsenko was sacked by parliament again.
Less than a year after Mr Yanukovych became president, Mr Lutsenko was jailed as part of an investigation on charges of abuse of office.
They involved giving illegal bonuses and perks to his driver at the expense of the state and misspending money during celebrations of Police Day.
In February 2012, he was sentenced to four years in jail for abuse of office and embezzlement.
Mr Lutsenko maintains his innocence, saying he was the victim of a show trial staged by his opponents.
Europe's top human rights watchdog, the Council of Europe, criticised the ruling, saying the former interior minister did not receive a fair hearing.
In April 2013, President Yanukovych pardoned Mr Lutsenko amid reports of his ill health and following pressure from the West.
While behind bars, Mr Lutsenko remained an active blogger on pro-opposition Ukrayinska Pravda website, expressing his views on the current political situation.
He also says he read many books in prison and even posted an extensive list of 200 titles with annotations and comments.
Release and current ambitions
Upon his release from jail, Yuriy Lutsenko denied any ambitions to become a major opposition leader or run for the presidency.
"All I do will be aimed to support those democratic candidates who have already emerged," he said immediately after walking out of jail.
"I will do my best not to get in their way."
In April 2013, however, he set up a "civic movement" of his own, called the Third Ukrainian Republic, which could be a sign of growing political ambitions.
At the moment, however, Mr Lutsenko remains largely overshadowed by other opposition figures in Ukraine: boxing champion Vitali Klitschko from Udar party, Arseniy Yatsenyuk of Yuliya Tymoshenko's Fatherland and Oleh Tyahnybok from the far-right Freedom party.
Source: BBC News