After starting her career in theatre, Margolyes made the transition to film with a small part in the British comedy A Nice Girl Like Me (1969).

Subsequent credits include Yentl (1983), Little Shop of Horrors (1986), Little Dorrit (1988), I Love You to Death (1990), Immortal Beloved (1994), Different for Girls, Romeo + Juliet (both 1996), Magnolia, End of Days (both 1999), Being Julia, and Ladies in Lavender (both 2004).

Margolyes appeared in the television films Poor Little Rich Girl: The Barbara Hutton Story (1987), Orpheus Descending (1990), Stalin (1992), Cold Comfort Farm (1995), and The Life and Death of Peter Sellers (2004).

On stage, Margolyes toured her one-woman show, Dickens' Women, between 1989 and 2012, which earned her an Olivier Award nomination; starred as Sue Mengers in the Australian premiere of I'll Eat You Last (2014); and originated the role of Madame Morrible in Wicked (West End, 2006; Broadway, 2008).

[2][3][4][5] She was the only child of Joseph Margolyes (1899–1995), a Scottish physician and general practitioner from the Gorbals area of Glasgow,[6] and property-developer Ruth[2][7] (née Sandeman; 1905–1974),[8] daughter of a second-hand furniture dealer and auctioneer at Kirkdale, Liverpool, who later relocated to London.

[2][9][10] Her maternal great-grandfather, Symeon Sandmann, was born in the Polish town of Margonin, then part of the Kingdom of Prussia, which Margolyes visited in 2013.

Her paternal grandfather Philip Margolyes was born in the small Belarusian shtetl of Amdur, which at the time was in Grodno Governorate, Russian Empire.

[12] She represented Newnham College in the first series of University Challenge, where she may have been one of the first people to say "fuck" on British television;[13] she claims to have used the word in frustration on the show in 1963.

She also worked with the theatre company Gay Sweatshop and provided voiceovers in the Japanese TV series The Water Margin (credited as Mirium Margolyes).

[citation needed] In 1974, she appeared with Kenneth Williams and Ted Ray in the BBC Radio 2 comedy series The Betty Witherspoon Show.

In a 2011 interview on The Graham Norton Show, in regard to her Potter costars, Margolyes said that she got on well with Maggie Smith, but rather bluntly admitted that she "didn't like the one that died", referring to Richard Harris.

[36] Margolyes played recurring character Prudence Stanley in the Australian-based TV series Miss Fisher's Murder Mysteries from 2012 to 2015.

[citation needed] In January 2018, Margolyes hosted a three-part series for the BBC titled Miriam's Big American Adventure, highlighting the citizens of the United States and the issues facing the country.

[45] On 5 November she appeared on BBC One's The Graham Norton Show, where she discussed the book, explaining that it was written only because she "was paid an enormous amount of money".

[55] As of 2012[update] they were dividing their time between homes in London and Kent in England, Robertson, New South Wales in Australia, and Montisi in Italy.

However, in the 1970s, she joined the Workers Revolutionary Party with other actors and Equity members such as Vanessa Redgrave, Frances de la Tour, and Tom Kempinski.

In August 2015, she was a signatory to a letter criticising The Jewish Chronicle's reporting of Labour leader Jeremy Corbyn's alleged associations with antisemites.

[66][67] Later in the month, along with other public figures, she signed a letter supporting Corbyn and describing him as a "beacon of hope in the struggle against emergent far-right nationalism, xenophobia, and racism in much of the democratic world".

[70] In November 2023, Margolyes said during another appearance on The Graham Norton Show that her position had changed after a discussion with Zoe Terakes, a trans Australian actor, and that she no longer believed that grammar was paramount over making someone happy by using their preferred pronouns.

"[75] On 6 April 2024, a video by Margolyes was published by The Jewish Council of Australia criticising the Israeli government on its ongoing invasion of the Gaza Strip and calling on Jews to "shout, beg, scream" for a ceasefire.

He's changed us Jews from being compassionate and caring and do unto others as you would have them do unto you into this vicious genocidal nationalist nation, pursuing and killing women and children.

[78] Author and comedian David Walliams says he used Margolyes as a model for the title character in his children's book Awful Auntie after an argument with her during a stage production, though he stressed that he has nothing against her and is a fan of her work.

[79] Wallace & Gromit[clarification needed] – Beryl Notes Margolyes was appointed Officer of the Order of the British Empire (OBE) in the 2002 New Year Honours for Services to Drama.