Negus studied arts and journalism at the University of Queensland. Negus attended Indooroopilly State High School located in the suburb of Indooroopilly in Queensland.

Negus was a high school teacher before writing for The Australian and The Australian Financial Review. He served as press secretary for Attorney-General Lionel Murphy. He became most prominent, however, as a reporter for This Day Tonight, a pioneering current affairs show on the ABC which began in 1967 and continued through the late 1960s and into the 1970s, and later in the heyday of the Australian 60 Minutes from 1979 until 1986, and then hosted Today until 1990.

From 1992 until 1999, he hosted the ABC's foreign-themed current affairs Foreign Correspondent. After this project he went to live in Italy for several years.

In 2002, Negus returned to the ABC and hosted the early evening timeslot show George Negus Tonight covering "trends and issues with an Australia-wide team of reporters and producers". The show was axed in November, 2004.

In 2005, Negus went on to host Dateline on the SBS network.

Negus has also written several books, including one based on his time in Italy, and co-wrote a series of children's books with Kirsty Cockburn, his partner, in the early 1990s. His latest, successful book is The World from Islam, an investigation of the Islamic world.

Negus lives on a farm near Bellingen on the New South Wales northern coast, with his partner, Kirsty Cockburn, herself a journalist and a collaborator on many of Negus's projects, and their sons Ned and Serge. Negus is a fan of association football and a former board member of the national governing body Soccer Australia, as it was known at the time.