[2] In the late 19th century, Bishop John Hennessy of Dubuque petitioned the Vatican to create a separate diocese for southern Iowa.

In 1934, Gerald Bergan of the Diocese of Peoria was appointed the third bishop of Des Moines by Pope Pius XI.

In 1967, after Biskup was in Des Moines for only two years, Paul VI appointed him as coadjutor archbishop for the Archdiocese of Indianapolis.

[9] In 1979, while on his American tour, Pope John Paul II visited the diocese on the suggestion of Joe Hays, a farmer in Truro and on the invitation of Dingman.

Pope Francis in 2019 named William Joensen from the Archdiocese of Dubuque as the next bishop of Des Moines.

In January 2023, the diocese released new restrictive policies on the treatment of transgender individuals in diocesan churches, schools and other facilities.

In 2003, Bishop Charron permanently suspended three diocesan priests from ministry due to sexual abuse allegations: Albert Wilwerding, John Ryan, and Richard Wagner.

[14] In 2015, Pope Francis laicized Reverend Howard Fitzgerald, who was credibly accused of sexually abusing a minor in the previous decades.

[16] In April 2019, Bishop Pates released a list of nine diocesan priests with credible accusations of sexual abuse of minors.

[17] In March 2020, the diocese announced that it was suspending Reverend Robert Grant, a professor at St. Ambrose University in Davenport, from teaching and practicing ministry after a sex abuse allegation surfaced.

[18][19] Grant allegedly committed the abuse while working at St. Albert High School in Council Bluffs in the early 1990s.

[18][19] In November 2020, the diocese determined that Grant's sexual misconduct took place when the accuser was above the age of consent.