In 2001, Brodie-Sangster's first acting role was in a BBC television film, Station Jim.
He subsequently appeared in a few more television films, including the lead roles in Bobbie's Girl, The Miracle of the Cards (based on the story of Craig Shergold) and Stig of the Dump.
He won the "Golden Nymph" award at the 43rd Annual Monte Carlo Television Festival for his role in the miniseries Entrusted.
Brodie-Sangster's first major theatrical film was Love Actually (2003), in which he played Sam.
He was nominated for a Golden Satellite Award and a Young Artist Award for his role in the film.

Brodie-Sangster next appeared in a television adaptation of the novel Feather Boy and played a younger version of James Franco's Tristan in the film version of Tristan & Isolde.
Among other things, Brodie-Sangster takes part in a (child's) sword fight in the film.
Brodie-Sangster next starred in the commercially successful film Nanny McPhee (2005) as the eldest of seven children.

In 2007, he appeared in a two-part story (Human Nature and The Family of Blood) in Doctor Who as schoolboy Timothy "Tim" Latimer, and guest-starred in the Big Finish Doctor Who audio dramas The Mind's Eye and The Bride of Peladon.
His voice lowered during filming of the Doctor Who episodes.
He also starred in the film adaptation of Valerio Massimo Manfredi's historical novel The Last Legion, released in 2007.
That same year he voiced the character of Ferb Fletcher in the Disney Channel animated series Phineas and Ferb.
He appeared in the 2008 miniseries Pinocchio, filmed in Italy, as Lampwick.

In March 2008, it was announced that Brodie-Sangster would star in Steven Spielberg's CGI motion capture film The Adventures of Tintin as the title character of Hergé's comic books.
Brodie-Sangster left the project after scheduling difficulties when filming was delayed in October 2008 and the role was given to Jamie Bell.

Also in 2008, Brodie-Sangster had a role in director Jane Campion's film Bright Star, a love story about John Keats and his lover Fanny Brawne.
He also starred as Paul McCartney in Nowhere Boy, a film directed by award-winning artist Sam Taylor-Wood, about the teenage years of John Lennon.

Brodie-Sangster appeared as Casey in the film Some Dogs Bite about a boy who wants to keep his family together.
Casey takes his baby brother out of foster care and, with the help of his older brother, goes in search of their father.
Brodie-Sangster appeared in the Irish film Death of a Superhero, based on the novel by Anthony McCarten.

Additionally, Brodie-Sangster plays Liam in the 2011 film The Last Furlong.
In April 2011, he made a guest appearance as Adam Douglas in an episode of British detective drama Lewis.
In 2012, he starred in The Baytown Outlaws and in Ella Jones's short film, The Ugly Duckling, the third installment of the Tales trilogy of reworked fairy tales from More Films.
From 2013 to 2014, he played the role of Jojen Reed in the HBO series Game of Thrones.
In 2015, he began providing the voice of John Tracy in ITV's remake of Gerry Anderson's puppet series Thunderbirds Are Go (2015–present).

Brodie-Sangster played Newt in the 20th Century Fox Maze Runner trilogy, including The Maze Runner (2014), Maze Runner: The Scorch Trials (2015), and Maze Runner: The Death Cure (2018).
In BBC2's 6-part television adaptation of Wolf Hall (on BBC2 from 21 January 2015), Brodie-Sangster portrayed Rafe Sadler, the ward of Thomas Cromwell.

On 24 May 2017, a 15-minute sequel to Love Actually was released with Brodie-Sangster as part of the cast.
It was shown on the BBC as part of Comic Relief's Red Nose Day and titled Red Nose Day Actually and brought back a large number of characters from the first film.

In 2017, Brodie-Sangster began portraying Whitey Winn in the Netflix western drama miniseries Godless (2017).
In 2001, Brodie-Sangster's first acting role was in a BBC television film, Station Jim. He subsequently appeared in a few more television films, including the lead roles in Bobbie's Girl, The Miracle of the Cards (based on the story of Craig Shergold) and Stig of the Dump. He won the "Golden Nymph" award at the 43rd Annual Monte Carlo Television Festival for his role in the miniseries Entrusted. Brodie-Sangster's first major theatrical film was Love Actually (2003), in which he played Sam. He was nominated for a Golden Satellite Award and a Young Artist Award for his role in the film.
Brodie-Sangster next appeared in a television adaptation of the novel Feather Boy and played a younger version of James Franco's Tristan in the film version of Tristan & Isolde. Among other things, Brodie-Sangster takes part in a (child's) sword fight in the film. Brodie-Sangster next starred in the commercially successful film Nanny McPhee (2005) as the eldest of seven children.
In 2007, he appeared in a two-part story (Human Nature and The Family of Blood) in Doctor Who as schoolboy Timothy "Tim" Latimer, and guest-starred in the Big Finish Doctor Who audio dramas The Mind's Eye and The Bride of Peladon. His voice lowered during filming of the Doctor Who episodes. He also starred in the film adaptation of Valerio Massimo Manfredi's historical novel The Last Legion, released in 2007. That same year he voiced the character of Ferb Fletcher in the Disney Channel animated series Phineas and Ferb. He appeared in the 2008 miniseries Pinocchio, filmed in Italy, as Lampwick.
In March 2008, it was announced that Brodie-Sangster would star in Steven Spielberg's CGI motion capture film The Adventures of Tintin as the title character of Hergé's comic books. Brodie-Sangster left the project after scheduling difficulties when filming was delayed in October 2008 and the role was given to Jamie Bell.
Also in 2008, Brodie-Sangster had a role in director Jane Campion's film Bright Star, a love story about John Keats and his lover Fanny Brawne. He also starred as Paul McCartney in Nowhere Boy, a film directed by award-winning artist Sam Taylor-Wood, about the teenage years of John Lennon.
Brodie-Sangster appeared as Casey in the film Some Dogs Bite about a boy who wants to keep his family together. Casey takes his baby brother out of foster care and, with the help of his older brother, goes in search of their father. Brodie-Sangster appeared in the Irish film Death of a Superhero, based on the novel by Anthony McCarten.
Additionally, Brodie-Sangster plays Liam in the 2011 film The Last Furlong. In April 2011, he made a guest appearance as Adam Douglas in an episode of British detective drama Lewis. In 2012, he starred in The Baytown Outlaws and in Ella Jones's short film, The Ugly Duckling, the third installment of the Tales trilogy of reworked fairy tales from More Films. From 2013 to 2014, he played the role of Jojen Reed in the HBO series Game of Thrones. In 2015, he began providing the voice of John Tracy in ITV's remake of Gerry Anderson's puppet series Thunderbirds Are Go (2015–present).
Brodie-Sangster played Newt in the 20th Century Fox Maze Runner trilogy, including The Maze Runner (2014), Maze Runner: The Scorch Trials (2015), and Maze Runner: The Death Cure (2018). In BBC2's 6-part television adaptation of Wolf Hall (on BBC2 from 21 January 2015), Brodie-Sangster portrayed Rafe Sadler, the ward of Thomas Cromwell.
On 24 May 2017, a 15-minute sequel to Love Actually was released with Brodie-Sangster as part of the cast. It was shown on the BBC as part of Comic Relief's Red Nose Day and titled Red Nose Day Actually and brought back a large number of characters from the first film.
In 2017, Brodie-Sangster began portraying Whitey Winn in the Netflix western drama miniseries Godless (2017).
Thomas Brodie-Sangster