In 2006, after featuring in minor credits in Motivos personales and Obsesión, Casas landed his first television main role in the teen drama SMS: Sin Miedo a Soñar and also debuted in the big screen in Summer Rain.

[1] Casas acquired a larger clout owing to his appearance in the television series Los hombres de Paco, as part of a popular love triangle together with Hugo Silva and Michelle Jenner.

[1] His early film career, featuring in box-office darlings such as Sex, Party and Lies (2009), Brain Drain (2009), and Three Steps Above Heaven (2010), consolidated after his performance as bad boy Hache in the latter title, which earned him wide popularity in Spain.

[1] He went on to feature in starring roles in films such as Unit 7 (2012), I Want You (2012; the sequel to Three Steps Above Heaven), The Mule (2013), Witching & Bitching (2013), Ismael (2013), My Big Night (2015), Palm Trees in the Snow (2015), Toro (2016), The Invisible Guest (2016), The Bar (2017), The Skin of the Wolf (2017), The Photographer of Mauthausen (2018), Bye (2019), The Occupant (2020), and The Paramedic (2020).

[9] Mario Casas began his acting career with episode appearances in television series Obsesión (English: Obsession), Motivos personales (Personal Motives) and Mujeres (Women).

During the late 2013 and early 2014, he went to Colombia and Chile for his second film project in English called Los 33 (The 33) with Antonio Banderas and Juliette Binoche, a story based on the Chilean mining accident that occurred in 2010.

[18] Mario Casas is reported to have been in relationships with several fellow castmates including Erika Sanz [es], Amaia Salamanca, María Valverde, Berta Vázquez, Blanca Suárez, and Déborah François.