Mulholland received a degree in Communications in 1983 from Dublin City University and he also studied for an Master of Arts in media and communications at California State University, Sacramento.
He has worked for most of his career with the Guardian Media Group. He worked as arts assistant at The Independent from 1987-1988, then briefly for London Daily News in the same role. He co-founded Listings Limited in 1988 as the deputy editor, providing arts and entertainments listings to newspapers.
He joined The Guardian as assistant editor of the arts desk in 1990, then became media editor in 1994.
In 1998 he left The Guardian to manage the relaunch of Mirror Group Newspapers" Sporting Life, but his contract was ended after three months and before the launch after a disagreement over the management of the project He rejoined the Guardian Media Group as deputy editor of The Observer in 1998, overseeing the magazines, sport, travel and culture sections.
He developed and launched the monthly food, sport and music magazines and lead the change of format to Berliner. Mulholland succeeded Roger Alton as editor in January 2008 (announced in October 2007), having read The Observer as a teenager, and reshuffled the paper"s editorial team
He closed the monthly sport, music and women"s magazines in 2009, and relaunched the paper in February 2010 with four sections and a reduced staff of 70 to reduce costs.
Mulholland faced criticism and calls for his resignation due to an article by pJulie Burchill published in The Observer on 13 January 2013 which was widely seen as transphobic. Mulholland responded on the comments page to what he described as "many emails protesting about this piece" and stated that he would be looking into the issue. On 1 June 2015, Muholland additionally became an assistant editor of The Guardian in one of the first appointments made by Katharine Viner, the new editor-in-chief of Guardian News and Media.