His parents, Gillian (née James) and Peter Griffiths (Ioan uses Gruffudd, the more traditional Welsh version of the surname[citation needed]), were both teachers.

He was an accomplished oboist in his teens,[6] achieving a Grade 8 level in the ABRSM music examinations[7] and playing in the South Glamorgan Youth Orchestra for several years,[8] but gave it up once acting took up most of his time.

"[9] His television work includes playing the character Pip in the BBC TV production of Charles Dickens' Great Expectations (1999), Lt. John Feeley in BBC One's Warriors (1999) and architect Philip Bosinney in ITV's adaptation of The Forsyte Saga (2002).

[3][13] In 2007, he starred in the historical drama Amazing Grace as William Wilberforce, the British abolitionist, receiving critical acclaim for the role.

In 2009, he starred alongside Josh Brolin in W., a biopic about the life of US President George W Bush, in which Gruffudd played Tony Blair.

[15] In early 2014, Gruffudd was among the stars of Wales in a short film from the BBC to mark the centenary of the birth of Welsh poet Dylan Thomas.

[16] Gruffudd débuted his new male lead of Dr Andrew Earlham, a respected surgeon and widowed father of a teenage son, on 11 September 2017, in ITV's new 6-part thriller miniseries, Liar.

Dr Earlham's world—personally and professionally—is torn asunder when his son's schoolteacher, Laura Neilson (Joanne Froggatt) accuses him of raping her after their first date, the details of which she cannot remember.

[17] The show is set and filmed in Brisbane and focuses on Gruffudd's character Dr. Harrow - a forensic pathologist with a total disregard for authority, and an unfailing empathy for the dead which helps him to solve the most bizarre cases.

[18][19] Apart from television and film work, he starred in the music video of Westlife's version of "Uptown Girl" (2001) alongside Claudia Schiffer.

[20] His other film credits include 102 Dalmatians (2000), Black Hawk Down (2001), The Gathering (2003), Fireflies in the Garden (2008), The Secret of Moonacre (2008), Sanctum, Horrible Bosses, Foster (all 2011), The Adventurer: The Curse of the Midas Box (2014), and San Andreas (2015).

[24] In an interview in 2020, Gruffudd said that working away from home meant that he and his wife had struggled to spend time with each other in the previous four years.

[28] On 2 August 2022, Gruffudd was granted a three-year permanent domestic violence restraining order against Evans.