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Seward was born in on May 16, 1801, in the small community of Florida, New York, in Orange County. He was the fourth son of Samuel Sweezy Seward and his wife Mary (Jennings) Seward. Samuel Seward was a wealthy landowner and slaveholder in New York State; slavery was not fully abolished in the state until 1827. Florida was located some 60 miles (97 km) north of New York City, west of the Hudson River, and was a small rural village of perhaps a dozen homes.

There were no primaries in 1860, no way to be certain how many delegates a candidate might receive. Nevertheless, going into the 1860 Republican National Convention in May in Chicago, Seward was seen as the overwhelming favorite. Others spoken of for the nomination included Ohio Governor Salmon P. Chase, former Missouri congressman Edward Bates, and former Illinois congressman Abraham Lincoln. Seward stayed in Auburn during the convention; Weed was present on his behalf and worked to shore up Seward's support. He was amply supplied with money: business owners had eagerly given, expecting Seward to be the next president. Weed's reputation was not entirely positive; he was believed corrupt by some, and his association both helped and hurt Seward. Enemies such as publisher and former Seward ally Horace Greeley cast doubts as to Seward's electability in the battleground states of Illinois, Indiana, Pennsylvania and New Jersey. Lincoln had worked hard to gain a reputation as a moderate in the party and hoped to be seen as a consensus second choice, who might be successful in those critical states, of which the Republicans had to win three to secure the election. Lincoln's men, led by his friend David Davis, were active on his behalf. As Lincoln had not been seen as a major candidate, his supporters had been able to influence the decision to hold the convention in his home state, and surrounded the New York delegation, pro-Seward, with Lincoln loyalists. They eventually were successful in gaining the support of the delegations from the other battleground states, boosting delegates' perceptions of Lincoln's electability. Although Lincoln and Seward shared many views, Lincoln, out of office since 1849, had not excited opposition as Seward had in the South and among Know Nothings. Lincoln's views on nativism, which he opposed, were not public. On the first ballot, Seward had 173 1/2 votes to Lincoln's 102, with 233 needed to nominate. Pennsylvania shifted its vote to Lincoln on the second ballot, and Seward's lead was cut to 184 1/2 to 181. On the third, Lincoln had 231 1/2 to Seward's 180 after the roll call, but Ohio changed four votes from Chase to Lincoln, giving the Illinoian the nomination and starting a small stampede; the nomination was eventually made unanimous. When word reached Seward by telegraph, by the accounts of witnesses, he calmly remarked that Lincoln had some of the attributes needed to be president, and would certainly be elected.
William H. Seward