Brendan Fletcher was born and raised in British Columbia, Canada. He made his acting debut in the lead role of Des, an 11-year-old on the wrong path in life in the TV movie Little Criminals (1995), which was filmed in Vancouver.
He has continued to work in both Canadian and American productions, with recurring and regular roles on TV shows such as The Adventures of Shirley Holmes (1996 to 2000), Caitlin's Way (2000 to 2001), Dice (2001), The Pacific (2010), Rogue (2014), Gracepoint (2014), Cardinal (2017), Arrow (2018 to 2019) and Siren (2019 to 2020).
Brendan played the role of Fryman in the Oscar-nominated film The Revenant (2015) alongside Leonardo DiCaprio.
In 2019, he played the starring role of Arthur Lambden in the Canadian film Brotherhood (2019).