Before entering the Senate, Farrell was the South Australian Secretary and the National President of the Shop, Distributive and Allied Employees Association union and a leader of Labor Unity in South Australia. Farrell first ran for parliament at the 1988 Adelaide by-election but was unsuccessful. In June 2007, Farrell won preselection for the first position on Labor's Senate ticket in the 2007 election and he was subsequently the first elected senator for South Australia at the general election. Following the 2010 federal election, he was appointed Parliamentary Secretary for Sustainability and Urban Water. On 25 March 2013, Farrell was promoted into the Outer Ministry as the Minister for Science and Research and the Minister Assisting on Tourism. On 1 July 2013 as part of the Second Rudd Ministry, Farrell was appointed the Minister for Sport as well as remaining Minister Assisting on Tourism. In 2011 Farrell was listed as number six on the top ten political fixers as identified by The Power Index website. Where the article states that Labor's former deputy leader, Ralph Clarke commented:
"He controls the pre-selection directly or indirectly of every MP in South Australia. If you want to get on, you get on with Don."
In 2012, he was again selected as the first candidate on Labor's Senate ticket in the 2013 federal election, causing some controversy as he defeated Penny Wong for the leading Senate position. At the time, Wong was a senior minister in the Second Gillard Ministry and a member of the Australian Cabinet. Anthony Albanese accused union powerbrokers of not listening to the electorate and instead focusing on its own ructions. He labelled the move as:
"...gross self-indulgent rubbish.... ....those who should care more about the party and less about themselves."
He stated that he would demand that Labor's national executive overturn the decision and promote Senator Wong to the number one spot. On 30 October 2012, Farrell stepped aside to give Wong the number one spot on Labor's senate ticket for the 2013 election. He was quoted as saying:
"I was concerned that the issue was damaging the Labor Party...... I was prepared to do a swap with Penny. This is a case whereby modern Labor can't be seen to be concentrating on our internals at the expense of what is going on out there in the electorate and what is expected."
Wong later expressed favourable sentiments about Farrell after his decision to stand aside:
"Throughout his career, Don has always put the Labor Party first and he has demonstrated that principle again today."
Farrell was subsequently defeated at the 2013 federal election and his term in the Senate ended on 30 June 2014. In January 2014 it was announced that Michael O'Brien offered Farrell his state seat of Napier, so that Farrell could contest the 2014 South Australian election, representing Labor. PremierJay Weatherill threatened to resign if Farrell was successfully preselected. A few hours later, Farrell withdrew his nomination. In 2016 Farrell was endorsed as a Labor candidate for the Senate in South Australia in the 2016 federal election, and was subsequently re-elected. Farrell opposes same-sex marriage and supports the view of "traditional marriage as being between a man and a woman". He has publicly stated that he will vote against marriage equality in the parliament regardless of the results of the Australian Marriage Law Postal Survey. However from 2019 he will follow the Labor Policy Platform from that time which will not permit a conscience vote on the issue.
