The event aims to raise money for its beneficiaries from donations from private citizens, organisations, businesses and corporations, as well as from special fundraising events held throughout the year and the public auction of up to two specially built Telethon homes, with one in the metropolitan area of Perth and one in a regional area of Western Australia.

In addition, Telethon has hosted a number of high profile international guests including Michael Jackson, Phyllis Diller, Carrie Fisher, and the Harlem Globetrotters.

A number of Australian guests, such as Hugh Jackman, Chris Hemsworth, Samara Weaving, Ryan Kwanten and Troye Sivan, have also appeared on Telethon before achieving international fame themselves.

[9][7][10][11] Musical guests are also an integral part of the weekend's entertainment; over the years, notable international performers during Telethon have included Sir Cliff Richard, Harry Connick Jr., Whitney Houston, Stevie Wonder, Tina Turner, Julian Lennon, Sammy Davis Jr. Petula Clark and Céline Dion.

In 1994 Jeff Newman was awarded for services to charity and fundraising through his work with Telethon and the Variety Club of Western Australia.

[17] In 1998 Stuart Wagstaff was appointed a Member of the Order of Australia (AM) for service to the community, particularly through Telethon by raising funds for charities that support children's medical research.

[18] TVW previously broadcast one-off telethons for bushfire relief in 1961, and to raise funds for Christmas care packages sent to Western Australian soldiers serving in Vietnam in 1966 and 1967.

[20] It was inspired by the success of the first MDA Labor Day Telethon hosted by Jerry Lewis in the United States in 1966, and the Good Friday Appeal in Melbourne.

[21] Cruthers first brought up the idea with then-CEO of Princess Margaret Hospital, James Clarkson during a round of golf at Lake Karrinyup Country Club, who suggested that the focus should be on facilitating medical research.

[9][21][19] Although all of the station staff agreed to volunteer their time to host the event, the first Perth Telethon has been described as chaotic: the station was open to the public for the first time resulting in hours-long queues of people wanting to get in, there were no computers so pledges and receipts were written out by hand, and anyone who pledged more than $2,000 ($25,377 in 2020) received a follow-up phone call to ensure it was not a hoax.

[9] The first Telethon also featured an infamous segment where guests Stuart Wagstaff, Johnny O'Keefe, Bobby Limb and Graham Kennedy, who were shirtless at the time as part of a dare, had to scramble to find their clothing before then-Premier of Western Australia David Brand made an appearance at the station.

Michael Jackson appeared on the October 1985 Telethon as part of a deal with Western Australian millionaire Robert Holmes à Court (who owned the television station at the time) to acquire ATV Music Publishing.

That same year also saw Telethon Avenue, a street in the Kings Square precinct of the Perth City Link project, named in recognition of the organisation.

Due to ongoing border restrictions, the 2020 broadcast also focused more on WA-based performers and personalities, though celebrities from the eastern states and overseas, and those from Seven's shows still featured during the event via pre-recorded segments.

The fundraising event was promoted as an opportunity for families to come together following the easing of pandemic restrictions and the cancellation of the 2020 Perth Royal Show earlier in the year.