McGregor was born in Perth and raised in Crieff. His mother, Carol Diane (née Lawson), is a retired Teacher at Crieff High School and latterly deputy head Teacher at Kingspark School in Dundee. His father, James Charles Stewart "Jim" McGregor, is a retired physical education Teacher and careers master at Morrison's Academy in Crieff. He has an older brother, Colin (born 1969), a former Tornado GR4 pilot in the Royal Air Force. His uncle is actor Denis Lawson and his aunt by marriage was Actress Sheila Gish, which makes him a step-cousin of Gish's Actress daughters, Kay Curram and Lou Gish.

Six months prior to his graduation from Guildhall, McGregor won a leading role in Dennis Potter's six-part Channel 4 series Lipstick on Your Collar (1993). Not long afterwards, he starred in the BBC adaptation of Scarlet and Black (also 1993) with a young Rachel Weisz, and made his film debut in Bill Forsyth's Being Human (1994). For his role in the thriller Shallow Grave (also 1994), he won an Empire Award. The film was his first collaboration with Director Danny Boyle. His international breakthrough followed with the role of heroin addict Mark Renton in Boyle's Trainspotting (1996), an adaptation of Irvine Welsh's novel of the same name.

From November 1998 to March 1999, McGregor starred as Malcolm Scrawdyke in a revival of David Halliwell's Little Malcolm and His Struggles Against the Eunuchs, directed by his uncle, Denis Lawson. The production was first staged at the Hampstead Theatre before transferring to the Comedy Theatre in London's West End. In November 2001, McGregor made a cameo appearance in The Play What I Wrote.

McGregor starred in Moulin Rouge! (2001) as the young poet Christian, who falls in love with the terminally-ill courtesan Satine (Nicole Kidman). He starred alongside Renée Zellweger in Down With Love (2003). He also portrayed the younger Edward Bloom in the critically acclaimed film Big Fish (2003) alongside Albert Finney, Jessica Lange, Alison Lohman and Billy Crudup. In the same period, he also received critical acclaim for his portrayal of an amoral drifter mixed up with murder in the drama Young Adam (also 2003), which co-starred Tilda Swinton.

McGregor is involved in charity work, including UNICEF UK since 2004 and GO Campaign. During the Long Way Round journey in 2004, McGregor and his travelling companions saw some of UNICEF's work in Ukraine, Kazakhstan, and Mongolia, and during the Long Way Down trip in 2007, he and Charley Boorman did some work for UNICEF in Africa. McGregor hosted the annual Hollywood gala for the GO Campaign in 2009 and 2010. He has worked with the Children's Hospice Association Scotland, as featured in Long Way Down. In 2012, he travelled with UNICEF immunization workers to remote parts of India, Nepal and the Republic of Congo for a BBC2 documentary entitled Ewan McGregor: Cold Chain Mission. In June 2015, McGregor read Hans Christian Andersen's "The Little Match Girl" for the children's fairytales app GivingTales in aid of UNICEF, together with other prominent figures such Roger Moore, Stephen Fry, Joan Collins, Joanna Lumley, and Michael Caine.

From June 2005 to April 2007, McGregor starred alongside Jane Krakowski, Douglas Hodge and Jenna Russell in the Donmar Warehouse revival of Guys and Dolls after it transferred to the Piccadilly Theatre in London. He played the leading role of Sky Masterson. McGregor received the LastMinute.com award for Best Actor for his performance in 2005, and he was nominated for a Laurence Olivier Award for Best Actor in a Musical in 2007.

He narrated the Fulldome production Astronaut (2006), created for the National Space Centre. Around the same time, he also narrated the STV show JetSet (also 2006), a six-part series following the lives of trainee pilots and navigators at RAF Lossiemouth as they undergo a gruelling six-month course learning to fly the Tornado GR4, the RAF's primary attack aircraft. McGregor starred opposite Colin Farrell in the Woody Allen film Cassandra's Dream (2007), and he co-starred with Jim Carrey in I Love You Phillip Morris and appeared in Amelia (both 2009) alongside Hilary Swank. He played "the ghost" — the unnamed main character — in Roman Polanski's political thriller The Ghost Writer (2010). He portrayed Camerlengo Patrick McKenna in Angels & Demons (also 2009), the film adaptation of Dan Brown's novel of the same name. At the 2011 Seattle International Film Festival, he was awarded with the SIFF Golden Space Needle Award for Outstanding Achievement in Acting.

In 2007, on an episode of Parkinson, McGregor stated that he had given up alcohol after a period where he was arguably a functioning alcoholic, and that he had not had a drink in seven years. In 2008, he had a cancerous mole removed from underneath his right eye.

In 2010, McGregor was appointed by the French government as a Chevalier dans l'Ordre des Arts et Lettres (Knight of the Order of the Arts and Letters). McGregor was appointed an Officer of the Order of the British Empire (OBE) in the 2013 New Year Honours for services to drama and charity.

McGregor appeared in a two-part BBC documentary in April 2012 entitled Ewan McGregor: Cold Chain Mission in which he travels by motorbike, boat, plane and foot to deliver vaccines to children in remote parts of India, Nepal and the Republic of Congo. The trip was part of his work as a UNICEF Ambassador.

McGregor won a Golden Globe Award for Best Actor – Miniseries or Television Film for his dual performance in the 2017 FX anthology series in the third season of Fargo and received Golden Globe nominations for Best Actor – Musical or Comedy for both Moulin Rouge! and Salmon Fishing in the Yemen. McGregor has also starred in theatre productions of Guys and Dolls (2005–07) and Othello (2007–08). He was ranked number 36 on Empire magazine's "The Top 100 Movie Stars of All Time" list in 1997. In a 2004 poll for the BBC, McGregor was named the fourth most influential person in British culture. He has been involved in charity work and has served as an ambassador for UNICEF UK since 2004. In 2016, he received the BAFTA Britannia Humanitarian Award.

In a June 2015 interview, McGregor indicated that a long discussed South American trip with Boorman was still in the planning stages, but he expected that an excursion through the Baja California Peninsula would take place first.

He reprised his role as Mark Renton in T2: Trainspotting 2 (2017). McGregor played Lumiere in the live action version of Disney's Beauty and the Beast (also 2017), directed by Bill Condon. Filming began in May 2015 at Shepperton Studios in London, and the movie was released in March 2017. He then starred in FX anthology series in the third season of Fargo (both 2017), which garnered him a Golden Globe Award for Best Actor – Miniseries or Television Film for his dual performance of Emmit Stussy and Ray Stussy at the 75th Golden Globe Awards. McGregor is set to play an adult version of Christopher Robin in a live-action film of the Winnie the Pooh franchise, directed by Marc Forster; co-starring with Hayley Atwell.

McGregor married Eve Mavrakis, a Greek-French production designer whom he met on the set of Kavanagh QC, in 1995. Together they have four daughters, one of them adopted from Mongolia. McGregor has a heart and dagger tattoo of the names of his wife and daughters on his right arm. The family lived in Los Angeles County, California, having relocated from London. With his children raised in his wife's Jewish faith, McGregor has said, "My involvement in religion has more to do with the Jewish faith now and not the Christian faith, which I was very vaguely brought up in". As of May 2017, he was estranged from his wife and dating Actress Mary Elizabeth Winstead, whom he met on the set of season 3 of Fargo in which they starred together. On 19 January 2018, McGregor filed for divorce from his wife, citing irreconcilable differences.