Voting 71 to 26, Castro's nomination easily cleared the simple majority needed for confirmation.
The Texas Democrat became the youngest mayor of a major U.S. city when he was elected in 2009 at the age of 34. As one of the party's rising stars, Castro's Hispanic identity and compelling biography as the grandson of Mexican immigrants have put him and his twin brother, Rep. Joaquin Castro, D-Texas, on many Democrats' shortlists as future presidential or vice presidential material.
Castro will replace Shaun Donovan, who was tapped by President Obama to replace newly installed Secretary of Health and Human Services Sylvia Mathews Burwell, formerly the director of the Office of Management and Budget.
Notable deaths of 2014 [PHOTOS]
Cyclist struck and dragged underneath car