St. Katharine Drexel was established July 1, 2001 with Father Paul E. Edwards as administrator. That same month, he conducted introductory meetings about the new parish and gave his vision for its future. Over 200 people attended the meetings, which were conducted in English and Spanish. That August, 20 parishioners each dedicated over 20 hours of service to the parish by preparing a mailing to over 14,000 households announcing its arrival. The first Masses were celebrated at Indian Trace Elementary School on Sunday, Sept. 16, 2001 — just days after the tragic events of the World Trade Center. Over 1,500 people attended: 669 at the English Mass and 889 at the Spanish Mass.

On Sunday, March 3, 2002, the parish held its first St. Katharine Drexel Feast Day Celebration at Markham Park. This consisted of an outdoor Mass, presided by Miami’s then Auxiliary Bishop Thomas Wenski, and followed by a parish picnic with lots of food and games. This event continues to be held each year around March 3, the feast day of St. Katharine Drexel.

As the parish approached its first anniversary, Father Edwards asked those early parishioners if they would be willing to become "Founding Members" by committing to the task of laying a solid foundation for the parish community and extending God's kingdom in this part of the world.

On Sunday, Sept. 15, 2002, after negotiations to rent space at 2700 Glades Circle, the parish moved into its own place of worship. Plans to build the new church were sadly interrupted by Father Edwards’ diagnosis in August 2005 with a brain tumor, which turned out to be malignant and led to his death, April 22, 2006.

From September 2005 to May 2006, the parish had two temporary administrators: Father Andrzej (Andrew) Pietraszko, who had previously been assigned to St. Katharine Drexel as deacon, became interim administrator until December 2005, when Father Jorge Bello was appointed to the position. At the end of May 2006, Father Pedro M. Corces was named administrator, becoming pastor March 25, 2007.

In April 2010, Father Corces was succeeded as pastor by Father Enrique Delgado, who worked very hard with parishioners to raise the money needed to build the parish’s first permanent home, a multipurpose building. Located on the parish’s permanent site, at 2501 South Post Road, the building was dedicated Feb. 16, 2014.

The parish has seen considerable turnover since its founding. When it started in 2002, the religious education program had 114 children registered. By 2012, the number had grown to 700. Some of the founding members have moved to other parts of the country, but this has been more than compensated by the influx of new parishioners.

On June 6th, 2022, Msgr. Enrique Delgado was succeeded as pastor by Fr. Omar Ayubi.

The total number of parishioners is currently estimated at 5294 families.