US Attorney General John Ashcroft, who had been under constant fire from pro-immigrant groups for his "tough tactics" since 9/11, and Commerce Secretary Don Evans, said to be very close to President George W Bush, resigned on Tuesday.
The resignations were announced by White House press secretary Scott McClellan, who said Bush had accepted the decisions.
In their letters to Bush, the two did not cite any specific reasons.
But Ashcroft said in his handwritten letter that he believed that the Justice Department would be well served by new leadership and fresh inspiration.
"I believe that my energies and talents should be directed toward other challenging horizons," he said.
Evans, a close friend of Bush from Texas, said, "While the promise of your second term shines bright, I have concluded with deep regret that it is time for me to return home."
Bush praised them and acknowledged their "tireless" work in making America safer.