The organisation said in a statement that Scott Blackmun is also resigning due to "ongoing health issues" as a result of his prostate cancer.
Mr Blackmun is leaving his post after eight years and received praise for bringing the 2028 Olympics back to Los Angeles, was also heavily criticised for the handling of Larry Nassar, the USA Gymnastics team doctor who was convicted of abusing more than 260 young women and girls.
USOC Chairman Larry Probst said in the statement: “Given Scott’s current health situation, we have mutually agreed it is in the best interest of both Scott and the USOC that we identify new leadership so that we can immediately address the urgent initiatives ahead of us".
Mr Blackmun was responsible for the establishment of the US Center for SafeSport and the development of the SafeSport initiative to protect athletes, however it was overshadowed with the revelation of Nasser's decades of abuse of USA Gymnastics team members and Michigan State University athletes.
Earlier in February 2018, US Senators Jeanne Shaheen and Joni Ernst called on him to resign after it was discovered he may have heard about the abuse allegations as early as September 2015 from concerned parents, but did not take measures to address the problem.
USOC members initially refused to heed the Senators' calls.
A Senate panel has also been established to investigate who knew about Nasser's abuse and to establish a timeline.
The panel announcement came just after legislation was passed by the full Congress that would require governing bodies of amateur athletes to immediately report any allegations of abuse to police and improve oversight of gyms, the organisations, and coaches involved in the sport.
Nasser has been sentenced up to 125 years in prison and had to listen to hundreds of his victim's give statements in court at his sentencing hearing.
Susanne Lyons, a former executive with Visa, is set to take over for Mr Blackmun.
The USOC said in its statement that last month Ms Lyons was selected as "chair of the USOC board’s working group addressing issues the Nassar case has brought to light. Since then, she has been leading the USOC’s efforts to ensure a process that is independent, transparent, sensitive and accessible".
Part of Ms Lyon's mission going forward includes implementing changes like ensuring increased funding for psychological counselling for survivors of Nassar's abuse as well as increasing funding for investigators in the SafeSport initiative, the USOC said in a news release.
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