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Frances O'Grady is to step down as general secretary of the Trades Union Congress after nine years in post.
Ms O'Grady said leading the UK's trade union movement had been "the greatest honour of my life".
On election in 2013, she became the first woman to lead the TUC - the UK's umbrella group for unions, which represents millions of workers.
Labour's Sir Keir Starmer said she was a "great champion for working people" and her departure would be a huge loss.
A union official nearly all her working life, Ms O'Grady joined the TUC in 1994 after growing up in an active trade unionist family.
During the pandemic, she worked with the government on the furlough scheme, which saw workers receive a guaranteed income while huge swathes of the economy were shut down due to Covid.
During her career, she campaigned to introduce the national minimum wage, argued for rebalancing the economy after the 2008 financial crash, led on negotiations over working standards at the London 2012 Olympics, and pushed for more women to join the union movement.
Announcing her intention to step down at the end of the year, the 62-year-old said: "Unions are a force for good in British society.
"I am proud of what we achieved during the pandemic - from securing furlough to keeping people safe at work, championing equality and keeping vital services running.
"The last decade has been turbulent - with three general elections, two anti-trade union bills, an EU referendum and a pandemic to contend with.
"But on every occasion unions have risen to the challenge and fought for working people."
Her replacement will be elected at the TUC's annual meeting in September.
Profile: Frances O'Grady
- Born in Oxford in 1959, one of five children in a working-class family of Irish origin
- Her upbringing was steeped in trade unionism, with relatives active in the movement
- She joined the TUC in 1994 and went on to lead a push to recruit more women members
- Appointed deputy general secretary in 2003 and elected as general secretary 10 years later