Anglican missionaries took advantage of the spread of the empire to prosleytise to Native Americans and African Americans. Motivated by a desire to bring the gospel to so-called heathens and halt the spread of Catholicism, Cambridge men travelled to North America, the Caribbean, West Africa, and India to spread Protestantism. If they chose not to head abroad, they instead provided donations to missionary organisations, such as the Society for the Propagation of the Gospel in Foreign Parts, or assisted in the administration of plantations owned by these organisations. As Cambridge missionaries and dergymen encountered enslavement, prominent University figures became increasingly interested in debates concerning and morality the efficacy of Indigenous and African slavery. Some fellows were actively sceptical of the moral grounds for slavery, whilst others believed that enslavement was grounded in Christian belief. Rather than emerging in the era of abolition, scepticism and debate about the moral foundations of enslavement were consistent features of British intellectual life for over a century.

The slavery debates at Cambridge did not end with the emancipation of enslaved people in the Caribbean and India in 1843. In fact, undergraduates, fellows, and professors increasingly turned their attention to enslavement in the United States of America. Cambridge-educated abolitionists, such as Edward Strutt Abdy and Alexander Crummell, sought to mobilise opinion in both America and Britain against the persistent power of the enslaver class in the Southern United States. The outbreak of the American Civil War (1861–1865) inspired growing sympathy amongst educated British elites, including those at Cambridge, towards the Confederate cause, with many comparing American enslavers to landed British gentry in order to build camaraderie between British and American elites. The Confederacy, in turn, sought to lobby university men and mobilise student opinion in their favour to further the cause of Confederate diplomatic recognition in Britain.

The growing professionalisation of the law and the natural sciences owed much to the spread of the empire – and Cambridge intellectuals would benefit more than most from these processes. Natural philosophers travelled across the empire amassing botantical, geological, and antiquarian collections and expanding scientific knowledge, with much of the credit for their findings owed to local enslavers or enslaved Africans. Britons with financial investments in slave-trading organisations also donated to found professorships. In the case of the law, experts in international law and treaty-making, particularly Sir Nathaniel Lloyd, applied their expert knowledge to cases concerning piracy, plantation holdings, and imperial companies. As with missionary organisations, the problem of enslavement continued to be a source of debate in the eighteenth century, as philosophers of natural law and rights considered the ethical justifications for racial enslavement.

Following the abolition of the slave trade, Cambridge men turned their intellectual attentions to the institution of slavery as a whole. Nevertheless, students, alumni, and fellows were torn on how best to create an empire of free labour and on the prospects for freed people of colour in post-emancipation societies. The early nineteenth century was a colorful era of experimentation as Cambridge activists sought to gradually achieve abolition without precipitating the violence and rebellion that characterized the Haitian Revolution, whilst Black and radical white abolitionists advocated for an immediate end to racial slavery. Historians have long ignored this phase of Cambridge debate on enslavement post-1807, which has resulted in a historiography of Cambridge abolitionism which overemphasizes its radical nature. In reality, a growing conservatism dominated this period of abolitionist thought at Cambridge – particularly as some Cambridge fellows and alumni continued to eschew pro-slavery rhetoric.