In addition to his television work Micallef has appeared on stage, most notably in the Australian production of Boeing Boeing and on radio as the co-host of Melbourne station Vega 91.5 FM's morning program. He is also a published author with three books: Smithereens (2004, re-released 2011), Preincarnate (2010) and The President's Desk (2014).

Micallef was born in Adelaide, South Australia, and is of Maltese and Irish descent. His father worked for a company that sold parts for Volvos and his mother was employed at the Adelaide Bank.

As a child, Micallef lived in Clovelly Park and attended St Bernadette's School in St Marys then St Joseph's Catholic School in Mitchell Park (now Sacred Heart College Middle School) before moving on to Sacred Heart Senior College where he was the College Captain.

Micallef studied law at the University of Adelaide, where he was frequently involved in comedy revues, often involving Francis Greenslade and Gary McCaffrie, with whom he continues to work.
In 1972, having three younger sisters taking ballet classes, ten-year-old Micallef was often asked to help out when a dance routine required a boy. The following year he auditioned for the Bunyip Children's Theatre and over the next four years participated in plays that they performed in the Scott Theatre during school holidays. In 1976 he doubled for Humphrey B. Bear for personal appearances.
Micallef was a practising solicitor for ten years in the field of insurance law before making the decision to move to Melbourne and pursue a full-time career in comedy in 1993.
He relates the story that, while working as a solicitor, he talked so much about making a career change and becoming a comedian that his wife Leandra gave him an ultimatum: she marked a date on a calendar and told him to quit his job and become a comedian by that date or never talk about it again.
Following early TV appearances on Theatre Sports (1987) and The Big Gig (1989), in early 1993 Micallef was offered a job writing for the Jimeoin show which was soon followed by an offer to also write for the sketch comedy show Full Frontal where six months later he took on the role as co-producer with Gary McCaffrie. In 1994, Micallef became a full-time cast member of Full Frontal, where he became well known for characters such as Milo Kerrigan, Nobby Doldrums and a send-up of Italian male model Fabio. Micallef recalls that the show was a good introduction to television comedy because, with an ensemble cast, its success did not hinge on his performance and he had more freedom to make and learn from mistakes. However, he was frustrated with the lack of control he had over his work in the series as well as the repetition of characters and gags.
Micallef's role on Full Frontal led to a 1996 special Shaun Micallef's World Around Him and three seasons of the two-time Logie Award-winning ABC series The Micallef Program (1998–2001), which he co-wrote and produced with long-time writing partner Gary McCaffrie. Since the series' end he has created and starred in two short-lived television series, the sitcom Welcher & Welcher (2003) and the variety show Micallef Tonight (2003), and devised a series of telemovies, BlackJack (2003–present).
Micallef has also had acting roles in the television series SeaChange (2000), Through My Eyes (2004) and Offspring (2010) as well as supporting roles in the films Bad Eggs (2003), The Honourable Wally Norman (2003), The Extra (2005), Aquamarine (2006) and The King (2007). In 2006, he was a recurring guest on the Network Ten Improvisational theatre show Thank God You're Here.
In 2007, along with partners McCaffrie and Michael Ward, Micallef developed the satirical comedy program Newstopia, which he hosted. The show began airing on 10 October 2007 on SBS and in August 2008 it was announced that a third series had been commissioned. In 2009, Micallef joined the Ten Network and hosted Talkin' 'Bout Your Generation, which aired for four seasons.
In 2012, Micallef began hosting ABC1's Shaun Micallef's Mad as Hell.
He co-created Mr & Mrs Murder, a crime comedy television series for Channel Ten which aired in 2013, and starred in the lead role of Charlie Buchanan alongside Kat Stewart. Also that year, Micallef signed on to voice the artificially intelligent robot REEF in the Australian feature length science fiction film Arrowhead (2014).
In September 2005, Micallef began hosting the breakfast show "Shaun, Beverley and Denise" on Melbourne radio station Vega 91.5 FM with comedian Denise Scott and television presenter Beverley O'Connor. In July 2006, comedian Dave O'Neil took over as host and the show was renamed "Dave and Denise with Shaun Micallef". Micallef left the network on 23 November 2007.
Micallef released a book, Smithereens, which was published in 2004 and contains a collection of prose, poetry and plays. He describes it as a collection of "all sorts of bits and pieces I have written". His second book, a novella titled Preincarnate, was released in 2010.
In October 2014, Micallef released his third book, The President's Desk: An Alt-History of the United States; a semi-fictitious history, told from the perspective of the Resolute desk.
With Micallef's 2009 move to the Ten Network's Talkin' 'Bout Your Generation, a sudden and unprecedented rise in his popularity within the Australian mainstream has been observed. His contract with the program marks his first long-term position in a commercial network and has raised his profile in commercial television. The extent of this has been demonstrated with celebrity appearances on Rove McManus's Rove, Are You Smarter Than a 5th Grader? and on 9am with David & Kim. In 2010, he was voted most popular presenter at the annual Logie Awards.
Micallef currently lives in Williamstown, Victoria, with his wife Leandra, whom he married in 1988, and their three sons.
Arrowhead (2014) – REEF (voice)
The Cup (2011) – Lee Freedman
The King (2007) – Colin Bednall
Aquamarine (2006) – Storm Banks
The Extra (2005) – Paul Ridley
Bad Eggs (2003) – Premier Cray
The Honourable Wally Norman (2003) – Ken Oats
The 13th House (2003) – Sir
Silly Billy Don't Touch That! (unknown)
The Ex-PM (2015) - Andrew Dugdale
Shaun Micallef's Stairway to Heaven (2014) - himself
Live On Bowen (2014) - himself (guest)
It's a Date (2013-) – Roland (Season 2, Episode 2)
Danger 5 (2012, 2014) - Principal
Mr & Mrs Murder (2013) – Charlie Buchanan
Shaun Micallef's Mad as Hell (2012–) – host
Mollusks (2011) – Easty (voice)
The Bazura Project's Guide To Sinema (2011) – MK-Ultra (voice)
Laid (2011–2012) – G-Bomb
A Quiet Word With ... (2011) – himself (guest)
Offspring (2010) – Lachlan
Shaun Micallef's New Year's Rave – host
Are You Smarter Than a 5th Grader?
The Chaser's War on Everything (2009) – himself (guest in the Rudd song sketch)
Rove (2009) – himself (guest)
Melbourne International Comedy Festival (2009) – host
Talkin' 'Bout Your Generation (2009–2012) – host
Good News Week (2009) – himself (guest)
Spicks and Specks (2008) – himself (guest)
Newstopia (2007–2008) – himself
Dogstar (2007) – narrator
Thank God You're Here (2006–2007) – various (semi-regular guest)
The Shambles (2006) – (guest cameo)
Through My Eyes (2005) – Jack Winneke
BlackJack (2003–2007) (writer)
Micallef Tonight (2003) – himself (also writer)
Welcher & Welcher (2003) – Quentin Welcher (also writer and producer)
SeaChange (2000) – Warwick Munro
The Micallef Program (1998–2001) – various (also writer and producer)
Under Melbourne Tonight (1996) - Guest
Shaun Micallef's World Around Him (1996) – various (also writer and producer)
The Glynn Nicholas Show (1996) (writer)
Full Frontal (1994–1997) – various (also writer and producer)
Jimeoin (1994) – various (also writer)
The Big Gig (1989) (writer)
Boeing Boeing (2008) – Bernard
Good Evening - Sketches from Dudley Moore and Peter Cook (2010)
The Odd Couple (2016)
Dave and Denise with Shaun Micallef on Vega 91.5 FM (2005–2007)
Hamish & Andy on Fox FM (a guest twice)
Pete and Myf (with Newstopia writer Richard Marsland on Triple M (guest two times)
Get This appeared on the final show in the first hour
The Comedy Crystal Set – Adelaide University Radio, Co-host
The President's Desk (2014)
Preincarnate (2010)
Smithereens (2004)
His Generation (2009)
2012: Named Comedian of the Year at the GQ Men of the Year Awards, which celebrates the country's finest actors, comedians, sportsmen, musicians and creative visionaries.
2008: Won Aria Award Best Comedy Release – The Expurgated Micallef Tonight: The Very Best of Shaun Micallef's Short-Lived but Brilliant Tonight Show
2010: Won Most Popular Presenter and nominated for the Gold Logie at the Logie Awards for his role on Talkin' 'Bout Your Generation.