Melling attended Hendon School and then Mill Hill School. He trained at the Sue Nieto Theatre School in North-West London and is currently attending the London Academy of Music and Dramatic Art, where his productions include The Provoked Wife, King John, Antigone, Plenty and Sisterhood. He is a member of the National Youth Theatre.

He appears in the forthcoming film Harry Potter and the Deathly Hallows Pt1. In 2009 he made his stage debut as "Swiss Cheese" in a revival of Mother Courage and her Children at the National Theatre, alongside Fiona Shaw who played his mother "(Aunt) Petunia Dursley" in the Harry Potter films.

On 11 October 2009, it was announced that Melling had lost a lot of weight since his appearance from the last Harry Potter film that he was now "unrecognizable". He lost so much weight that his role as Dudley Dursley was almost recast. However, it was announced that he will be reprising his role as Dudley Dursley, and that he would be wearing a fat-suit to show Dudley's chubbiness . Melling commented positively about the change, "I can now shed the child actor thing, like the fat, and start a new career, because no one sees me as Dudley."