[1] Although he found negotiations for Oregon territory "agreeable," Dayton condemned the annexation of Texas as an attempt to spread slavery and regarded the Mexican-American War as dishonorable.

[1] Following the conflict's conclusion, Dayton supported the Wilmot Proviso and voted against the 1850 Compromise, believing it conceded too much to pro-slavery interests.

In 1856, Dayton was selected by the nascent Republican Party as their first nominee for Vice President of the United States over Abraham Lincoln at the Philadelphia Convention.

In France, Dayton was part of a successful lobbying campaign to prevent the government of Napoleon III from recognizing the independence of the Confederacy or allowing Confederate use of French ports.

[2] His son, William Lewis Dayton Jr. (1839–1897), graduated from Princeton in 1858 and served as President Chester A. Arthur's Ambassador to the Netherlands from 1882–1885.