Mr Cox's departure had been widely expected amid the handover to the new White House administration.
President Barack Obama has nominated Mary Schapiro of the Financial Industry Regulatory Authority to replace Mr Cox.
According to Bloomberg, the chairman leaves the regulator after one of the most turbulent periods in its 74-year history.
Under Mr Cox, the SEC was criticized for being too passive towards Wall Street. It also lost influence following the collapse of Bear Stearns and Lehman Brothers - and the conversion of Goldman Sachs and Morgan Stanley into commercial banks, the news agency said.
Last September, Mr Cox introduced the SEC's ban on the short selling of financial stocks. He later told the Washington Post that the ban was his greatest mistake.
In December, it was also revealed that the SEC had apparently failed to detect the $50 billion fraud allegedly carried out by Bernard Madoff.
Mr Cox said he was "gravely concerned" at the agency's failure to follow up on "credible and specific" allegations regarding Mr Madoff.
SEC commissioner Kathleen Casey is expected to be act as chairman until the Senate confirms Mr Cox's successor, Bloomberg noted.