Fatal Invention is about the biologization of the constructed, political category of race. Roberts defines race and race-based slavery as two distinct historical and political categorizations. Human populations across the world have historically categorized one another and also enslaved one another. The political category of race and its entanglement with enslavement, however, is a specifically modern “invention.”

Roberts demonstrates that, across cultures and time, humans have tended to categorize their own in-group as different from, and often superior to, other human populations. Humans have also, across cultures and history, enslaved one another. Yet race-based taxonomies are different from other human taxonomies of difference in that they insist on intrinsic difference that is immutable and deny any interchange between groups. In turn, unlike older forms of slavery, the race-based slavery of the United States was distinct in the inability of individuals to free themselves, of their own accord, from enslavement (aside from becoming a fugitive and fleeing to a place where slavery was outlawed): Slavery was for life. In addition, slavery was codified as racially based and inherited through the mother. Women were not only enslaved for their entire lives but also condemned to pass this legal status to their children.