When Katharine was 21, her mother was diagnosed with cancer. Katharine nursed her through three years of intense suffering. During this time she frequently thought that Christ might be calling her to the religious life. After Emma’s death, Katharine wrote to Bishop O’Connor about it. He advised her to “Think, pray and wait.”
Francis Drexel died suddenly in 1885. According to his will, the three sisters inherited the income from his estate, not the principal during their lifetime. The principal would go to their children, but if no children survived them, the money was to be distributed to the charities he listed. In 1887, Katharine and her two sisters went to Rome and had a private audience with Pope Leo XIII. Kneeling at his feet, Katharine pleaded for a missionary priest to be sent to the Indians of the United States. The Pope responded: “Why not, my child, yourself become a missionary?” Katharine told her sisters she did not know what the Pope meant and she was very frightened and sick.
She had thought about becoming a contemplative religious, devoting her life to prayer and giving her wealth to the support of the missions. What the Pope said was a new angle; this was not the contemplative life to which she felt inclined.
Msgr. Joseph Stephan, Director of the Catholic Bureau of Indian Missions, introduced Katharine and her sisters to the plight of the Native Americans. Traveling with him and with Bishop O’Connor, the young women visited several remote reservations in 1887 and 1888. They met with tribal leaders and witnessed the dire poverty endured by the people.
Katharine began building schools on the reservations, providing food, clothing and financial support. Aware also of the suffering of the black people, she extended her love to them. During her lifetime, through the Bureau of Colored and Indian Missions, she supported churches and schools throughout the United States and abroad.