Mescal graduated with a Bachelor of Arts in Acting from The Lir Academy at Trinity College Dublin in 2017.

Upon graduating from The Lir Academy, Mescal was offered roles in two theatre productions, Angela’s Ashes and The Great Gatsby; he took on the latter and starred as the titular Jay Gatsby at the Gate Theatre in Dublin. He also played the Prince in a contemporary retelling of Hans Christian Andersen’s The Red Shoes at the same theatre that year. In 2018, Mescal landed the role of Lieutenant Langon in productions of The Plough and the Stars at the Lyric Theatre in London and the Gaiety Theatre in Dublin. He also played Bryan in the world premiere of the 2018 play Asking for It by Louise O’Neill. He appeared in the Rough Magic Theatre Company’s productions of A Midsummer Night’s Dream and A Portrait of the Artist as a Young Man for the Kilkenny Arts Festival and the Dublin Theatre Festival, respectively. Mescal also appeared in a commercial for Denny sausages that same year. In 2020, he starred in a production of The Lieutenant of Inishmore at the Gaiety Theatre.

Mescal starred in his first television role alongside Daisy Edgar-Jones in the drama series Normal People, an adaptation of the 2018 novel of the same name by Sally Rooney. It premiered in the UK on BBC Three on 26 April 2020, and in the US on Hulu three days later. He garnered acclaim as well as a nomination for the Primetime Emmy Award for Outstanding Lead Actor in a Limited Series or Movie for his performance. In July 2020, Mescal performed spoken word and sang with Dermot Kennedy at the London Natural History Museum. He also portrayed Cian in a short film Drifting, which premiered at the 2020 Galway Film Fleadh. Mescal starred in the Channel 5 miniseries The Deceived as well as the music video for the song “Scarlet” by The Rolling Stones the following month. He appeared in a virtual stage reading of the play This Is Our Youth by Kenneth Lonergan as part of a series to benefit the Actors Fund of America in October.