Before entering politics she enjoyed a 30-year career in the healthcare sector and set up her own international consultancy firm focusing on the health care sector. 
She ran as an independent in a council by-election in her home village of Yewhurst, Surrey in 2006, winning the long-standing Conservative Party seat. She was re-elected in 2011 and announced she was joining UKIP shortly after the 2011 election, but refused to stand down and fight a by-election . She lost her seat in 2015 after standing as the UKIP candidate in the election .
In 2013 she rose to national prominence after finishing second in the Eastleigh by-election, during which she called for a temporary ban on all immigration to prevent 'crime associated with Romanians'. She later apologised for her comments, and said she had not meant to 'generalise against every single individual born with a Romanian passport'. 
She was elected to the European Parliament in June 2014.
In December 2014, James was selected by North West Hampshire UKIP to be its candidate for MP. However, a few hours after making a speech at the UKIP Spring Conference in Margate, Kent, she stepped down from the Westminster candidacy 'for personal reasons'. 
She was ally of former leader Nigel Farage, and was elected as UKIP new leader on 16 September 2016.Allies of Farage, including the influential donor and Brexit campaigner Arron Banks, had backed her. During her inaugural speech, she said her leadership would focus on ensuring Brexit was delivered. 'Until that ink is dry, we’re still in,' adding 'we’ve only just won a heat, a heat in a 28 member states Olympics competition to leave the European Union.'
She also issued a warning to the PM, whom she called 'magpie May', claiming she had stolen UKIP policies, including backing for new grammar schools. She addressed her, saying:
- 'When you try and bury UKIP, when you throw everything at us…just remember where the best ideas that you steal where they came from and in all likelihood where they will come from again in the future.' 
James explained that despite her support from party members she was not backed by colleagues. She will however, continue as a UKIP MEP for South East England.
- 'It has become clear I do not have sufficient authority, nor the full support of MEP colleagues and party officers to implement the changes I believe are necessary and upon which I based my campaign.'
- She caused controversy after praising Russian President Vladimir Putin for his 'strong leadership' in an April 2015 interview with Iain Dale. She said: 'I admire him from the point of view that he’s standing up for his country. He’s very nationalist. I do admire him'. She later clarified that she had made the comments before Russia’s controversial military intervention in Syria, but insisted: 'He's been one of the most patriotic leaders the world has ever seen. I stand by what I said.'  Her other comments suggested he and UKIP may share common ground over their disagreements with the EU, and she seemed to be justifying his invasion of Crimea.
- 'He has issues with the way the EU encouraged a change of government in the Ukraine which he thought put at risk and put in danger the Russian population in that country.' 
Affiliations as of 2014
- Non-executive director of ProVen VCT (a fund for private healthcare companies managed by Beringea LLP, a specialist private equity fund manager), for which she receives 500 to 1000e gross a month.
- HFMA (Healthcare Financial Management Association): Commercial advisor, for which she receives 500 to 1000e gross a month.
- Waverley Borough Council - Elected Councillor, for which she received an average of 400e a month. 2007 - May 2015 
- Iduna Ventures - Director / company secretary (unpaid)
- Healthcare policy consultancy (unpaid) 
- Diane JAMES, European Parliament, accessed 06 October 2016.
- Diane James becomes UKIP leader, BBC News, 16 September 2016. Accessed 04 October 2016.
- Reiss Smith, Who is Diane James? Everything you need to know as Ukip leader QUITS after just 18 days, Express, October 5 2016, accessed October 6 2016.
- Waverley Borough Election Results 2015, Waverley Borough, accessed 06 October 2016
- UKIP candidate Diane James drops out of election race, BBC News, 28 February 2015. Accessed 06 October 2016
- Josh Lowe, UKIP'S DIANE JAMES REPLACES NIGEL FARAGE AS LEADER, Newsweek, 16 September 2016. Accessed 06 October 2016.
- Rowena Mason and Peter Walker, Diane James quits as Ukip leader after just 18 days in role, The Guardian , 4 October 2016, accessed same day.
- Mikey Smith, Ukip's Diane James: 'I admire Vladimir Putin for standing up for his country', The Mirror, 9 April 2015. Accessed 06 October 2016.
- Declaration of Members’ Financial Interests, European Parliament, accessed 06 October 2016.