The 59-year-old former Washington governor was approved by unanimous consent, Roll Call reported.
The approval had been expected since the Commerce, Science and Transportation Committee had given Locke, a Democrat, a thumbs-up with a 25-0 vote at the conclusion of his March 19 confirmation hearing, CQ Politics reported.
Locke assured the panel the Commerce Department would steer clear of any political pressures when conducting the 2010 Census, which will be used to determine congressional districts and the apportionment of House lawmakers.
A free-trader, Locke said he would endeavor to open markets for American-made goods and firmly enforce U.S. trade laws.
Before he settled on Locke, Obama first selected New Mexico Gov. Bill Richardson, who withdrew after his nomination was clouded by a federal grand jury investigation over "pay for play" allegations involving a campaign donor, and Sen. Judd Gregg, R-N.H., who pulled out after deciding his political philosophy didn't jibe with that of Obama on fiscal policy.