The Cork native picked up the accolade for his role in the Christopher Nolan directed Oppenheimer on a hugely successful night for Irish film, which also saw the Dublin based Element Pictures winning in four categories, including a best actress award for Emma Stone.
Murphy's win for Best Actor, which was one of seven awards picked up by Oppenheimer on the night, saw the Peaky Blinders star receive a standing ovation while accepting the award. Other awards include Best Director for Christopher Nolan, and Best Supporting Actor for Robert Downey Jr.
"I'm a little bit overwhelmed", Murphy said while accepting the award.
The actor also paid tribute to director Christopher Nolan, "every single crew member, every single cast member - you carried me through", as well as his fellow nominees, declaring, "I'm in awe of you guys".
The humble star also thanked his family, "Yvonne McGuinness, my partner in life and art", and "my two boys, Malachy and Aran, who are sitting up there - I love you so much".
"I'm a very proud Irishman standing here tonight", he stated. "We made a film about the man who created the atomic bomb, and for better or for worse, we're all living in Oppenheimer's world, so I would really like to dedicate this to the peacemakers everywhere".
"Go raibh míle maith agaibh".