Founded in 1869 and chartered as a private medical college in 1881, UNMC became part of the University of Nebraska System in 1902.

[8] UNMC's academic, local, state, and federal partnerships have expanded with the initiation of the National Ebola Training and Education Center (NETEC).

[13] In 2016, UNMC was awarded a $19.8 million grant from the Office of the Assistant Secretary of Preparedness and Response in the U.S. Department of Health & Human Services.

Among the reasons behind the move were concerns about outbreaks of viruses, infectious diseases, and an environment where a biological terrorist attack is a possibility.

The grant will create the Great Plains IDeA-CTR Network, a collaboration involving nine institutions in four states: Nebraska, North Dakota, South Dakota and Kansas[16] In 2020, UNMC and Nebraska Medicine were enlisted to support a federal operation that evacuated 57 Americans from Wuhan, China, during an epidemic of novel coronavirus, SARS CoV-2.

[17] Thirteen Americans were repatriated to University of Nebraska Medical Center on February 17, from the Diamond Princess off the coast of Japan.

[18] The process, shared with hospital systems across the U.S., allowed multiple reuse of N95s when personal protective equipment was in short supply.

UNMC was named a Fulbright U.S. Scholar Program Top Producing Institution for the 2019–2020 and 2020–2021 academic years by the U.S. Department of State's Bureau of Educational and Cultural Affairs.

[28] The Buffett Cancer Center is a joint project with UNMC's primary clinical partner, Nebraska Medicine.