Democrats praised the 55-year-old Sotomayor as a mainstream moderate. But most Republicans voted against her, saying she'd bring personal bias and a liberal agenda to the bench.
Senators took the rare step of assembling at their desks on the Senate floor for the historic occasion, rising from their seats to cast their votes.
She replaces retiring Justice David Souter, a liberal named by a Republican president, and she is not expected to alter the court's ideological split.