Beginning his career as a child actor, Butterfield first achieved recognition as the lead of the historical drama film The Boy in the Striped Pyjamas (2008).

[citation needed] Butterfield started acting at age seven at the Young Actors Theatre Islington.

[8] In that same year, aged ten, Butterfield played the lead role in The Boy in the Striped Pyjamas.

Herman thought Butterfield's performance was outstanding, but only decided to cast him after auditioning hundreds of other boys, "so no stone was left unturned".

[9] Herman and producer David Heyman were looking for someone who was able to portray the main character's innocence, so they asked each of the children what they knew about the Holocaust.

In 2018, Butterfield was cast in the main role of Otis Milburn on the Netflix comedy-drama series Sex Education.

In late 2012, Butterfield co-designed a turn-based video game for iPad with his father and brother called Racing Blind.

[23] He is an enthusiastic player of competitive Super Smash Bros. and has signed with esports team Panda Global under the tag "Stimpy".

[27][28] In 2023, Butterfield played in the annual Soccer Aid charity football match, raising money for UNICEF.