Smith becomes the first Republican nominee considered since the legislature last fall invoked the "nuclear option" in abolishing the need for a two-thirds majority for judicial nominations to end debate.
In the procedural vote just after noon, the Senate voted 75 to 23 to end debate on the nomination. Fifty Democrats and 23 Republicans supported cloture, while 22 Republicans and one Democrat, Jeanne Shaheen of New Hampshire, voted no.
Several hours later, the Senate confirmed Smith to the bench, 69 to 31.
Smith will be the first federal trial judge to sit on the bench in Easton, Pa., in more than a decade. His nomination was slowed by progressives, who were opposed to his anti-abortion statements as a candidate for the House of Representatives in the 1990s.
The Senate also confirmed Judge Gerald A. McHugh Jr., a Democrat, for the Eastern District of Pennsylvania, Judge M. Douglas Harpool for the Western District of Missouri, and Judge Christopher Reid Cooper, to serve on the federal bench in D.C.