The parish traces its foundation to 1872, when the Irish Catholics of Iowa City and the surrounding countryside organized themselves and set about forming a new parish. A church building was acquired in the winter of that year. On January 4, 1873, the Iowa City Daily Press reported: "The Irish portion of the Catholic Church here bought the old Trinity Church and they will have a parish and a priest of their own."

On March 23, 1873 Rev. M. V. Rice offered the first Mass in the remodeled structure on Dubuque Street near Burlington Street.  On August 31, 1876 the parish obtained the property on Court and Linn Streets.  Ground was broken in October 1877 and the cornerstone laid on June 13, 1878.  Although the church lacked many finishing touches, the first Mass was celebrated on February 2, 1879.  St. Patrick, known as the Catholic Irish church, was built for $18,000 in an economic period when cattle were selling at $4.25 per hundredweight.

On March 14, 1885 the cornerstone was laid for a new Catholic school.  In 1896 the capacity of the parish school doubled and the parish dedicated its parish hall, known as St. Brendan's Hall.

The rectory was built in 1908; the convent for the sisters staffing the school was built in 1910.  The parish church was formally dedicated by Bishop Davis on January 29, 1916.  In 1922 classes were held in a new first class grade and high school building for a total cost of $150,000.

About the time the parish observed its 50th anniversary, a second priest was needed especially to look after the spiritual interests of the University of Iowa students.  An additional Mass was provided during the academic year for the students with the sermon adapted for their needs.

The parish flourished for several decades with many parish organizations, with men entering the seminary, women becoming sisters and many students graduating from the parish school.

During the early 1950s, Bishop Hayes asked the four Iowa City pastors to begin to formulate plans for a Central Catholic High School.  With strong leadership from Gathe Raymond Pacha, the people of Iowa City raised $900,000.  On August 31, 1958, Regina High School was dedicated.  In the fall of 1968, St. Patrick's school became known as the Iowa City Catholic grade school.  In 1969 the 7th and 8th grades were moved to Regina. Later, all the Catholic school students moved to Regina, and it became known as the Inter Parish Catholic Education Center. Religious education classes for the Iowa City parishes also started to be held at Regina.

On November 19, 1972, the people of St. Patrick's celebrated 100 years of the existence of their lively community of faith.

On January 14, 1986, through the efforts of Mark Boever and Gary Lanoue, a perpetual adoration chapel was begun in a room of the rectory basement. Thanks to the dedication of many faithful Catholics from the different parishes in Iowa City, adoration was able to be held 24 hours a day, 7 days a week. 

A Spanish Mass began to be celebrated regularly in the parish in 2004, initially presided by Fr. Bob Brownfield, and then later on by Fr. Rudy Juarez. 

On April 13, 2006, a series of tornadoes came through Iowa City during Holy Thursday evening Adoration.  St. Patrick's Church and its adjoining rectory were heavily damaged. Parishioners mourned the loss of the parish building where families had celebrated many milestones. Masses, Perpetual Adoration, other Sacraments, and social events were held temporarily at the Parish Hall located across the street from the destroyed church. 

Following the insurance settlement in November 2006, Bishop Franklin directed the parish to relocate.  Fourteen acres were purchased on the east side of Iowa City where housing growth was happening. After a successful Capital Campaign and the sale of both parcels of parish land on Court and Linn Streets, groundbreaking occurred in the new site on August 2, 2008. The new church building complex at 4330 St. Patricks Drive was dedicated by Bishop Martin Amos on November 29, 2009. 

Over the next few years, additions and improvements were made to the worship space and facility. Some of the stained-glass windows from the old church were refurbished and installed in the Daily Mass Chapel. A Marian Prayer Garden was dedicated in 2018 on the north end of the campus. New stained-glass windows and statues of various saints imported from Italy were installed in the Main Church in 2019.

The pandemic that started in March of 2020 forced the temporary closure of the Adoration Chapel. In September of 2021, it reopened with limited hours. In September of 2022, Adoration was moved to the Daily Mass Chapel, which was renamed the "Sacred Heart Chapel". 

A Plenary Indulgence was granted by Pope Francis for the Jubilee Year (150th Anniversary) of the parish. Bishop Thomas Zinkula presided at the opening Mass of the Jubilee on the First Sunday of Advent, November 28, 2021, and also at the closing Mass on Christ the King Sunday, November 20, 2022. 

The parish and her members are confident in the continuing intercession of her patron saint, whose “Breastplate Prayer” exhorts all the faithful to “arise today through God’s strength”.