The 59-40 vote was the second such successful confirmation vote Thursday, as the Senate follows through on a deal this week to advance long-stalled executive branch nominations.
Obama announced McCarthy as his pick for the EPA post on March 4, when he also nominated
Republicans blocked McCarthy's nomination as they sought answers to what they called "transparency requests" from the Obama administration over its environmental policy. Her status became part of a showdown between Senate leaders over delaying tactics that was resolved this week.
McCarthy is the fourth nominee confirmed as a result of the deal.
Currently an assistant administrator at the EPA, McCarthy also served stints in the administrations of Republican governors in Connecticut and Massachusetts. She will oversee the effort Obama announced in a recent speech on climate change to develop regulations designed to cut carbon dioxide emissions from existing power plants.