Bush called Spellings, his domestic policy adviser at the White House, a "dedicated reformer" who would continue the vital work of reforming the nation's schools.
"She knows the stakes are too high to tolerate failure," he said.
Bush said Spellings would help with his goal of expanding new achievement standards to high schools around the country.
Spellings crafted Bush's educational reforms while he was governor of Texas and had a major hand in fashioning the president's No Child Left Behind proposals, which became law in 2002.
Paige resigned from the Bush administration on Nov. 2, but his resignation letter was not made public until this week, when the White House released it together with those of Secretary of State Colin Powell, Energy Secretary Spencer Abraham and Agriculture Secretary Ann Veneman.
Attorney General John Ashcroft and Commerce Secretary Don Evans resigned a week earlier.
Spellings' nomination requires Senate confirmation.