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The primary issue that contributed to the outbreak of the Civil War was slavery. This institution was deeply entrenched in the Southern economy and social structure, leading to significant tensions between Northern and Southern states. The moral, economic, and political arguments surrounding slavery created deep divisions. The North generally opposed the expansion of slavery into new territories and states, catalyzing conflict over states' rights and federal authority.

As abolitionist sentiment grew in the North and pro-slavery sentiments firmly entrenched in the South, compromises such as the Missouri Compromise and the Compromise of 1850 were attempted to ease tensions but were ultimately unsuccessful. The election of Abraham Lincoln, who was viewed as an opponent of slavery's expansion, further provoked Southern states, leading to secession and the beginning of the Civil War.

The other options—industrialization, imperialism, and prohibition—while they may reflect significant historical contexts, were not direct triggers of the Civil War in the same way that slavery was. Industrialization influenced economic differences, but it did not cause the Civil War directly. Imperialism pertains more to global contexts and engagements rather than the domestic issues that spurred the Civil War. Prohibition is related to societal control over alcohol consumption and occurred later in American