Willard Saulsbury was born as the youngest of three sons of William and Margaret Smith Saulsbury, wealthy landowners in Kent County, Delaware, on June 2, 1820. Saulsbury prepared at Delaware College at Newark, and attended Dickinson College in Carlisle, Pennsylvania between 1839 and 1840 in the class of 1842 before leaving to study law.  His middle brother, Eli Saulsbury, also attended Dickinson.

He opened a practice in Georgetown, Delaware in 1845.  He became the attorney-general of Delaware in 1850, thus launching a career in politics as a Democrat.  He was present at the Democratic convention in Cincinnati in 1856 that nominated James Buchanan for the presidency; for his support he was appointed to the United States Senate in 1859.  He defended slavery but supported the preservation of the Union.  He vigorously opposed arrests for disloyalty in Delaware, supported Senator Bright of Indiana in his fight against expulsion for treason in 1862, and protested Lincoln's suspension of the writ of habeas corpus.