Forrest was born in Perth, Western Australia, the youngest of three children of Judith (née Fry) and Donald Forrest. His Father, grandfather (Mervyn), and great-grandfather (David) were all managers of Minderoo Station, which David had established in 1878 with his brothers, Alexander and John. John, Alexander, David, and Mervyn were all members of parliament for periods, with John serving as Western Australia's first premier. Forrest's early years were spent as a jackaroo at Minderoo, located in the Pilbara region south of Onslow. Minderoo was owned by the Forrest family until it was sold in 1998 by his Father due to relentless drought and debt, but it was bought back by Forrest in 2009.

After stepping down as Chief Executive Officer of FMG to reflect that he had been spending more than 50% of his time on indigenous philanthropy, and to hand leadership reins to former head of engineering company Thiess, Nev Power, he became Ambassador of the Australian Indigenous Education Foundation. Encouraged by the philanthropic work of the Rockefeller Group, Warren Buffett, and Melinda and bill Gates, Forrest founded the Australian Children's Trust with his wife Nicola in 2001. He also started the GenerationOne project, which was founded as a result of his hero and first mentor outside his Father, Scotty Black. Forrest obtained assistance from James Packer and Kerry Stokes, who each donated $2 million, along with the support of their respective media stations, Channel 9 and Channel 7. The organisation works with the Australian Children's Trust to help create sustainable solutions on addressing social disadvantage.

In 2003, he took control of Allied Mining and Processing and renamed it Fortescue Metals Group. He is still a major shareholder of FMG, through his private company, The Metal Group. Since then, the company has grown to possess three times the tenements of its nearest rival in Western Australia's iron ore rich Pilbara region. Fortescue holds major deposits at Mount Nicholas, Christmas Creek, Cloudbreak, and Tongolo. In 2007, he took control of a Niagara Mining, which owns tenements around Laverton, Western Australia. He was nominated as the 2011 Western region Ernst & Young Entrepreneur of the Year.

As of September 2007, Forrest had injected A$90 million into his children's charity. Philanthropic activity has included gifts to his alma mater, Hale School; participation in the St Vincent de Paul Society CEO sleepouts; and a gift from the proceeds of the sale of 5,000 tonnes (5,500 short tons) of iron ore to the Chinese earthquake relief effort. In October 2013 it was announced that Forrest was to donate A$65 million towards higher education in Western Australia. At the time the sum was believed to be the highest philanthropic donation in Australia, with most going toward funding scholarships. The Minderoo Foundation, Forrest's private foundation, was renamed as the Minderoo Group is to be expanded to include higher education contributions. The foundation has given A$270 million through the foundation since 2001.

With Kevin Rudd, Forrest launched the Australian Employment Covenant, which campaigns to have businesses hire indigenous Australians, as they could "add value" to Australian businesses because they were "professional and reliable and wonderful" and that there is no reason for indigenous disparity. He stated that he was dedicating time to the Covenant not because he was a "great guy", but that it was "good business". GenerationOne ran a series of television advertisements privately funded by Forrest, Packer and Stokes. Between 2008 and 2011, he obtained 253 Business signatories to his covenant. With then Prime Minister Rudd, Forrest planned to employ 50,000 Aborigines. As the two-year deadline approached, estimates put the number of Indigenous job placements under the scheme at around 2,800, clearly well short of the original goal.

After buying back the family property, Minderoo Station in 2009 Forrest acquired the adjoining properties, Nanutarra and Uaroo Stations in 2014. Forrest's total pastoral holdings in the Pilbara was then 7,300 square kilometres (2,819 sq mi). Meat processing company Harvey Beef was acquired by Forrest in 2014 for A$40 million. The company is the biggest exporter of beef in Western Australia and used to be the only one accredited to export to China until August 2014. Forrest acquired both Brick House Station and Minilya Station in 2015 for an estimated A$10 million, bringing his total pastoral holdings now to over 10,000 square kilometres (3,861 sq mi).

Forrest established the Walk Free Foundation in 2010 to fight modern slavery. In 2013 the organisation launched the Global Slavery Index ranking 162 countries "based on a combined measure of three factors: estimated prevalence of modern slavery by population, a measure of child marriage, and a measure of human trafficking in and out of a country". The Index estimates there are 29 million slaves worldwide, roughly half in India and Pakistan.

In June 2011, Allied Medical, of which Forrest owns 46%, was acquired by BioMD for over $20 million.

Forrest's daughter, Grace volunteered at an orphanage in Nepal and discovered the children she had looked after had been trafficked to be sex slaves in the Middle East. This distressed Grace and motivated her Father to act. Grace Forrest when 21 said at an interfaith meeting held at the Vatican, "I feel like a puppet for hundreds of thousands of girls who are voiceless – if I can stand for them, that is what I'm here to do."

Andrew and Grace Forrest took part in a meeting held in 2014 in the Vatican. There was a Joint Religious Leaders Declaration Against Modern Slavery which was signed by Pope Francis, Mata Amritanandamayi, Justin Welby, Thích Nhất Hạnh, K. Sri Dhammananda, David Rosen, Ecumenical Patriarch Bartholomew, Abraham Skorka, Mohamed ahmed El-Tayeb, Mohammad Taqi al-Modarresi, Basheer Hussain al-Najafi, and Omar Abboud: religious Leaders representing forms of Christianity, Judaism, Islam, Hinduism and Buddhism.

In 2017 Forrest was appointed an Officer of the Order of Australia for distinguished Service to the mining sector, to the development of employment and Business opportunities, as a supporter of sustainable foreign investment, and to philanthropy. 1

During his tenure at Fortescue, Forrest has been recognised for his work on the issue of indigenous disadvantage, using Fortescue Metals Group’s Vocational Training and Employment Centre to equip members of the indigenous communities for employment in the mining industry.