Strathairn appeared in supporting roles in many notable films such as A League of Their Own (1992), Sneakers (1992), The Firm (1993), The River Wild (1995), Lincoln (2012), Nomadland (2020), and Nightmare Alley (2021). He is a frequent collaborator with director John Sayles, who is a fellow graduate of Williams College.
On television, Strathairn is known for his recurring roles in The Sopranos (2004), Alphas (2011β2012), The Blacklist (2015β2016), Billions (2017β2019), and The Expanse (2018β2019). He received a Primetime Emmy Award win and a Golden Globe Award nomination for his performance in the HBO television film Temple Grandin (2010).