Earlier this year, Brady voiced his support for the proposal in the Illinois state legislature despite the GOP's official stance against it, the Chicago Tribune said. Brady said he made the endorsement as an individual, and not as the GOP chairman, but conservatives in the party quickly criticized him.
The party's central committee put together an exit strategy for Brady and a possible succession plan, the Tribune said.
His resignation marks the latest trouble for the struggling party that once held Illinois' governorship for nearly a quarter century.
After the November 2012 losses in the Illinois House and Senate, Brady, who served as chairman for three years, said Republicans need to be come more inclusive.
"If we come off as mean-spirited or angry or too dogmatic, then we don't attract people to the party," he said.