Before he joined the Justice Department, Whitaker had argued past year in his role as a CNN legal analyst that the Mueller investigation needed to be reined in, writing in an opinion piece that "investigating Donald Trump's finances or his family's finances falls completely outside of the realm of his 2016 campaign and allegations that the campaign coordinated with the Russian government or anyone else".
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Justice Dept. spokeswoman Sarah Flores said Whitaker would be in charge of all matters under the Dept. of Justice.
The 71-year-old served as the United States' 84th Attorney General from 2017 to 2018. "In my time at Attorney General, we have restored and upheld the rule of law -- a glorious tradition that each of us has a responsibility to safeguard".
His departure puts in jeopardy the special counsel investigation into Russian election interference, which Sessions had recused him.
Whitaker has run twice for elected state office in the past, once unsuccessfully as State Treasurer for Iowa in 2002 and once successfully as U.S. Attorney for the Southern District of Iowa, from 2004 to 2009.
Mr Trump has repeatedly pilloried his top law enforcement official since Mr Sessions stepped aside from the Russian Federation investigation in March 2017, allowing his deputy Rod Rosenstein to lead an inquiry that has dogged the White House.
"President Trump just removed Jeff Sessions". But with Sessions's resignation, that's changing.
Sessions said in a letter to Trump he resigned at the president's request. The piece goes on to cite law enforcement sources who say non-Russia-related leads that "involve Trump associates" are being referred to the special counsel "to encourage subjects of the investigation to cooperate".
Now Mr Trump has picked someone else - Matthew Whitaker.
Mr Rosenstein also has faced criticism from Mr Trump.
Republicans had repeatedly urged Mr Trump not to oust Mr Sessions, a conservative Republican former senator from Alabama, before the elections lest it create political fallout.