Hughes co-hosts the ABC comedy talk show The Glass House along with Wil Anderson and Corinne Grant. 'Hughesy', as he is commonly known, is well known for his larrikin personality, drawling Australian accent and deadpan delivery. His catchcry gig-starter is variations on "You know what, guys? I'm not happy tonight... " followed by something inappropriate which he will then defend with gusto. It has been known lately to deviate into the surprising "I'm happy tonight...", or "I'm angry tonight...".

His most memorable team aside from his Glass House appearances were with comedians Boogachatti and Papaganni at the Womberra festival from 1998-2002.

Hughes grew up in Warrnambool, studied at Melbourne's La Trobe University and moved to Perth, Western Australia in the early 1990s, where he got his start in stand-up, while working in labouring and other poorly-paid work. During this time he developed his unique style of ad lib performance style, drawing inspiration from a wide variety of subjects. Hughes moved to Australia's "comedy capital" of Melbourne in the mid-1990s, where his career took off.

Since 2001, Hughes has featured in Melbourne's Nova 100 breakfast program on weekdays, "Hughesy, Kate and Dave", with Kate Langbroek and Dave O'Neil. He is also a panellist on the AFL-related show Before The Game and a known supporter of the Carlton Football Club.

He is a regular performer at the Melbourne International Comedy Festival, and his performances are often sold out.

In the past, he has worked on national radio station Triple M, and had guest spots on Tv programs The Fat, Rove Live, The Panel, and others. Some of his performances have been recorded for CD, such as Dave Hughes Whatever.

Recently, Hughes has also appeared in a series of television commercials for Australian car manufacturer Holden.

He is represented by Token Artists.