Gale won a modeling competition in Perth at 18, After several years of modelling, Gale rose to fame when in 1999 was cast to appear in a series of advertisements for an Italian telecommunication company, Omnitel (now Vodafone Italy); she appeared in the company’s advertising until 2006. She was also retained by the Australian Tourist Commission in 2003 as ‘their face of Australia in Italy’. Gale has graced the covers of Australian Marie Claire, Grazia, Gioia, Italian and Australian GQ, Italian Maxim, Australian InStyle and featured in editorials for Australian Cosmopolitan and Vogue Italia.

Megan Gale has appeared in the Italian movies Vacanze di Natale 2000, Body Guards (as herself in both movies), and Stregati dalla luna (as Vivianna). She also had a cameo part in the 2005 movie Stealth where she played Dr. Orbit’s secretary. In January 2008, it was announced that she had been offered the part of Wonder Woman in the upcoming George Miller movie version of Justice League of America, before the project was put on hold and eventually cancelled. In August 2009, Gale completed filming a role in her first Australian feature film, the romantic comedy I Love You Too. Gale played Italian supermodel Francesca Moretti. Gale appeared in Miller’s post-apocalyptic action film Mad Max: Fury Road (2015).

In 2005, Gale became a guest reporter for Nine Network travel show Getaway from October 2005 to June 2006. She also worked with Mike Munro as co-host of the nine-episode Australian documentary TV show What a Year, which first aired on the Nine Network on 2 October 2006. Gale also appeared briefly on Australia’s Next Top Model, Cycle 4 in episode 4. She also appeared in cycle 6 (2010), in which the girls of that cycle were featured in Isola’s first fashion show.

Gale also became the National Ambassador for Kids Help Line in February 2005. In 2009, she was appointed the first official National Ambassador for The Red Cross.

Gale has modeled for Italian fashion houses including Gianfranco Ferré, Genny, Gai Mattiolo and runway work for Mariella Burani and Angelo Marani at Milan Fashion Week. Gale also favours many Australian designers, such as Colette Dinnigan, Kirrily Johnston, Lisa Ho, Willow and Alex Perry. In 2006, she was the fashion commentator for the Australian television awards, the Logies.

In January 2008, Gale announced her retirement from runway modelling after 15 years and walked the catwalk for the last time just weeks later at a David Jones winter collection launch in Sydney. Her final outfit was the Wonder Woman outfit she was to wear in the still-shelved film Justice League of America. In March 2011, Gale returned to the runway and closed Alex Perry’s 2011 Melbourne Fashion Festival show.

In 2010, Gale launched a swimwear label, Isola. The line is carried at department stores including David Jones.

August 2011 marked Gale’s 10th anniversary with department store David Jones, the longest held fashion contract in Australia. That same month, Gale became an ambassador for L’Oréal Paris, joining Beyoncé, Jennifer Lopez and Gwen Stefani. Gale appeared in a L’Oréal shampoo commercial in Australia, New Zealand and Italy.

In early 2011 Gale became the new host of Project Runway Australia where she would also serve as judge and executive producer of the design-based reality show. The new season premiered on 4 July 2011 on Arena TV. In 2016, Gale became a permanent judge on Australia’s Next Top Model.

In January 2011, Gale began a relationship with Richmond AFL footballer Shaun Hampson. On the 20 July 2017, the couple announced their engagement. They have two children; a son, River Alan Thomas, and a daughter, Rosie May Dee.