Mahoney left the agency last week to join Bartle Bogle Hegarty as a creative director. Brotherson joined Mustoes in November 2005.
He joined from Lowe, where he worked on the Stella Artois and Vauxhall accounts.
Brotherson's work for Stella Artois' Bock won silver awards at Creative Circle. Brotherson also spent five years at JWT, working on the agency's Smirnoff account among others.
Since joining Mustoes, Brotherson has been working on the £10 million launch campaign for the publishing company H Bauer's In the Know magazine. The television campaign, which broke last week, features Jeffrey Archer and Vanessa Feltz.
Following his promotion, Brotherson will work across a number of Mustoes' clients including Kia Motors, Lloyds Pharmacy and the Energy Saving Trust.
Nick Mustoe, the agency's chief executive, said: "There's a real energy and excitement that comes from a new appointment like this. We are lucky to have been able to plan for Mick Mahoney's successor in this way."
Brotherson added: "This is exactly the sort of opportunity I've been looking for. There is a core group of very talented people and clients at this agency. It's an agency that is genuinely about work and not the politics with the guy whose name is above the door. I couldn't be more excited."