Children will study the development of the trade, colonisation and how slavery was linked to the British empire and the industrial revolution.
Pupils will also study characters like Nigerian-born slave Olaudah Equiano, one of the prominent African figures who campaigned for abolition.
In history, World War I and WWII and the Holocaust are already compulsory.
The Department for Children, Schools and Families (DCSF) said all children aged 11 to 14 would be required to study the nature and effects of the slave trade, resistance to it and its abolition.
Children will also learn about the development of international trade and the impact of the British empire on different people in Britain and overseas. This will include pre-colonial civilisations and decolonisation.
Children's Minister Kevin Brennan said: "Although we may sometimes be ashamed to admit it, the slave trade is an integral part of British history.
"It is inextricably linked to trade, colonisation, industrialisation and the British empire.
"It is important that children learn about this and the links to wider world history, such as the American civil rights movement - the repercussions of which are still being felt today.
"That is why the slave trade will join the British empire, two world wars and the Holocaust as compulsory parts of the secondary school history curriculum from this September.
"Civil Rights struggle
Pupils will also be encouraged to look at the international and long-term impact of both the empire and slavery.
It is hoped that this will give pupils an understanding of the make-up of the UK today and put immigration, the Commonwealth and the legacy of the British empire into a clear historical context.
The DCSF says links could be made to emancipation, racial segregation and the 20th Century civil rights movement in the US.
Topic areas suggested by the Qualifications and Curriculum Authority include colonial rule in Africa, the abolition of slavery and the slave trade in the British empire, and the work of reformers such as William Wilberforce MP and Olaudah Equiano.
Historians argue slavery had a big impact on Britain's economy, with some saying it accounted for up to 5% of it at the height of the industrial revolution.
The curriculum has been developed with the assistance of the Understanding Slavery Initiative, which encourages teachers, educators and young people to examine the history and legacies of the transatlantic slave trade through museum artefacts.
The initiative's learning project manager, Ruth Fisher, said: "There's a lot of mis-education about slavery and it hasn't really been taught in schools at all.
"It's quite interesting in terms of today's history and what students need to know about the past to understand the present.
"You can't really talk about the history of the British empire without discussing this part of history."
She also suggested the sheer impact of slavery on the British economy and how involved it was with slavery had often been underplayed.
Chief executive of education charity DEA, Hetan Shah, said learning about slavery and associated issues such as trade and decolonisation was crucial so that young people could fully understand the shape of today's world.
"However, it is vital that the government provides better guidance and support to teachers so that they can teach these complex and difficult topics with confidence and success."