Richard Burr will quit during the investigation of stock trades he made before the sharp market downturn triggered by the coronavirus pandemic.
The Senate's Republican Majority Leader Mitch McConnell said Mr Burr contacted him on Thursday morning to inform of his decision to step aside during the investigation.
"We agreed that this decision would be in the best interests of the committee and will be effective at the end of the day tomorrow," McConnell said in a statement.
Mr Burr had denied wrongdoing and said he relied solely on news reports to guide decisions on stock sales, amid reports that he and other senators sold shares after private briefings on the risks of the coronavirus crisis.
The Republican senator turned over his phone to agents after they served a search warrant on him at his Washington home, the Los Angeles Times reported.
The news outlet cited an unnamed law enforcement official.
