As a musician, McDonnell was a member of Doctor Who–themed rock band Chameleon Circuit and the short-lived musical project Sons of Admirals until it disbanded in May 2011.

After setting up the YouTube channel, charlieissocoollike on 3 April 2007, McDonnell started posting video blogs (or vlogs) to a small audience.

[10] In January 2023, McDonnell posted a YouTube video in which she discussed her life and for the first time publicly, announced "I'm a transgender woman, [and] my pronouns are she/they".

Along with fellow vloggers Alex Day (Nerimon on YouTube), Liam Dryden (Littleradge), and former member Chris Beattie (CowInParachute), Chameleon Circuit released their self-titled debut album on 1 June 2009.

[23] In July 2010, their song Count the Shadows also appeared on DFTBA Records, Volume Two, a compilation sampler that was given for free in the grab bags at VidCon 2010.

[24] At the beginning of 2011, Chameleon Circuit, in their new line-up following the departure of Beattie and the addition of Ed Blann and Michael Aranda, began work on their second album Still Got Legs.

[25] In 2014, McDonnell and Dryden publicly denounced members Blann and Day, who both suspended their online presence following separate reported incidents of sexual abuse.

"[29] In 2010, McDonnell, along with three other YouTubers, Alex Day, Ed Blann, and Tom Milsom ("Hexachordal") formed a new musical project titled "Sons of Admirals".

[30] Their first single was released via YouTube on 14 June 2010 on McDonnell's channel: the group covered Cat Stevens' song "Here Comes My Baby", featuring all four members on vocals.

[36][37] On 30 September 2008, to celebrate her 18th birthday, McDonnell and Alex Day dyed and then shaved their hair off whilst live on BlogTV for a period of seven and a half hours in aid of Cancer Research UK.

Over the course of Chartjackers, McDonnell solicited lyrics, music, performers and stylists to record the final single and video via a YouTube channel named ChartJackersProject.

An unofficial charity single for Children in Need, the completed song was titled "I've Got Nothing" and was sung by vocalists Miranda Chartrand and Adam Nichols.

[45] In October 2013, it was announced that McDonnell was to play the main voice role along with Danny Wallace in Mike Bithell's indie video game Volume.

In 2014, McDonnell worked with the Home Office on their This Is Abuse Campaign, alongside other prominent YouTubers, in order to educate people about the importance of consensual sex.

[citation needed] In July 2010 McDonnell was signed up alongside KateModern star Emma Pollard and X Factor contestants Nicola and Fran Gleadall to present a TV show run by Piers Morgan called FirstTV, an offshoot of First News newspaper.

On FirstTV McDonnell did a few challenges like trying to break a Guinness world record by typing the alphabet on an iPad keyboard quickest and she got asked to tell a joke.

In November 2010, McDonnell was part of a group of YouTube videos called The Science of Attraction where she hosted a few experiments and had her body digitally swapped with somebody else's.