Marie Collins claims some Vatican staff are actively trying to stop the work of the Pontifical Commission for the Protection of Minors.
"I cannot at this point accept that there are still men in the Vatican, still men in those positions, that would resist the work to protect children, that still have the attitudes of 20 years ago," she said.
Collins, from Dublin, helped many other abuse survivors come forward after publicly revealing she was sexually abused as a child by a priest in a children's hospital during the 1960s.
She stressed in her resignation that Pope Francis himself has a "genuine wish" to root out all forms of abuse from the Catholic Church, but she accused some Vatican bureaucrats of not having them same desire.
"Despite the Holy Father approving all the recommendations made to him by the commission, there have been constant setbacks," she said in her resignation statement.
"This has been directly due to the resistance by some members of the Vatican Curia to the work of the Commission.
"The lack of co-operation, particularly by the dicastery [Vatican department] most closely involved in dealing with cases of abuse, has been shameful."
Rt Rev Diarmuid Martin, Catholic Archbishop of Dublin, said: "I have learned above all to see in her a person of integrity who is not afraid to chart her own course.
"Where things were wrong, she identified them and named them. When she felt uncomfortable, she was never tempted to take the easy path and remain quiet and I am certain that will be her position in the future."
