Witnesses say the attacker shouted "Britain First!" before shooting and stabbing the 41 year-old M-P.
Campaigning ahead of a vote next week on whether Britain will leave the European Union has been suspended after news of the death of Labour MP Jo Cox.
Ms Cox, who represented Batley and Spenborough in Britain's House of Commons, was attacked by a man in broad daylight as she met with local constituents in Birstall, West Yorkshire.
The temporary chief constable of the West Yorkshire Police, Dee Collins, has confirmed her death.
"At 1:48pm, Jo Cox was pronounced deceased by a doctor who was working with a paramedic crew that were attending to her serious injuries. This is a very significant investigation, with large numbers of witnesses that are being spoken to by police at this time. There is a large and significant crime scene, and then there is a large police presence in the area. A full investigation is underway."
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Tributes flow for 'great star' Jo Cox
The 41 year-old Ms Cox was elected to her position in 2015.
She had spent a decade working in various roles for the humanitarian organisation Oxfam across Europe and the United States.
She had previously been an adviser to the wives of two former Labour party leaders, including Sarah Brown, and was known for her work on women's issues.
Ms Cox was also known for her criticism of Britain's military involvement in the war against the self-proclaimed Islamic State, where she wanted what she called a "holistic plan."
A former colleague from Oxfam, Penny Lawrence, has described her as a champion for the vulnerable and the underprivileged.
"She was really passionate about people who were marginalised and so vulnerable, and she worked particularly closely on the Darfur campaign, really trying to ensure that people in Sudan were able to live and just have some kind of life. And I think her legacy is that, as individuals, we can do something and we can stand up for things that we think are really important in the world."
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Who was British Labour MP Jo Cox?
Ms Cox was married, with two young children, and divided her time between a houseboat on the River Thames in London and a home in her electorate.
Her husband Brendan has called on the public to come together and, in his words, "fight against the hatred that killed her."
British prime minister David Cameron announced he was cancelling an appearance at a pro-European Union rally planned in the British territory of Gibraltar.
He says politics has lost a rising star.
"This is absolutely tragic and dreadful news, and my thoughts are with Jo's husband Brendan and the two children, and their wider family. We've lost a great star. She was an MP, great campaigning MP, with huge compassion, with a big heart, and people are going to be very, very sad at what has happened. Dreadful, dreadful news."
Opposition Leader Jeremy Corbyn, who Ms Cox originally backed before changing her mind and voting for his opponent Liz Kendall, has described her as dedicated to public service.
"The whole of the Labour family is devastated tonight. Jo Cox has been killed doing her duty, doing her work, as a constituency MP. She's somebody who dedicated her life to human rights and to justice. She worked for anti-slavery campaigns, she worked for Oxfam, and she became an MP for the area where she was born and grew up and loved. In parliament, she was respected across the whole house as somebody with a deep commitment and deep passion for human rights and justice. Sadly, today, she died."
In 2010, a student stabbed an ex-cabinet minister in the stomach at his office in east London over his involvement in the 2003 Iraq war.
And in 2000, a man with a samurai sword murdered a Liberal Democrat councillor and seriously injured MP Nigel Jones.
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