In January 2022, Milhiser announced he would seek the Republican nomination for Illinois Secretary of State in the 2022 election.

[2] He started his legal career in the Sangamon County State's Attorney's office in 1997 and spent time in the juvenile, civil, and felony divisions before entering private practice in 2003.

On September 28, 2010, Milhiser was chosen by the Sangamon County Board to serve as the new State's Attorney until the 2012 general election.

[1][6] Milhiser, endorsed by the Sangamon County Republican Party, defeated Ron Tupy, longtime chief legal counsel for the Illinois Prisoner Review Board by a three-to-one margin in the 2012 Republican primary and defeated Democratic candidate and labor attorney Ron Stradt in the general election.

[8][9] On August 16, 2018, President Donald Trump announced his intent to nominate Milhiser to be the U.S. Attorney for the Central District of Illinois.