He was the Republican nominee for Governor of Pennsylvania in the 2018 election, losing by more than 800,000 votes to incumbent Democrat Tom Wolf.

[9] When Ron Miller, an incumbent member of the Pennsylvania House of Representatives, declared his intentions to run for the seat, Wagner charged the Republican Party with cronyism.

[1] He ran as an outsider, accusing party leaders of rigging the system against him,[5] and became the first write-in candidate to win election to the Pennsylvania State Senate in history.

[15] Working with Democratic senator Anthony H. Williams of Philadelphia, Wagner introduced Clean Slate legislation to automatically seal non-violent misdemeanor conviction records after someone remains crime-free for ten years.

[25] Wagner has also cosponsored bills that would prevent the use of state funds for non-abortion services, such as birth control and cancer screening, at Planned Parenthood.

[34] Prior to the 2018 gubernatorial election, Wagner declined to release his tax returns, suggesting that labor unions will use it to try to organize workers at his company.

[48] Wagner supported leasing Pennsylvania's wholesale liquor industry and privatizing the sale of alcohol, using $500 million in projected savings for education programs.

[45] Wagner also pledged to reverse Wolf's moratorium on the death penalty,[50] supporting restoration of capital punishment in Pennsylvania.

[52] Wagner proposed the creation of a fund to extent loans to people, especially those in poor communities, to open new businesses; he also criticized the state's existing public assistance programs.

[45] In a 2018 campaign appearance, a student challenged Wagner's claim that climate change is being caused by human body heat and asked whether his belief was the result of the money he received from the fossil fuel industry.

[4] Wagner expressed support for the Trump travel ban and called the Russia investigation "a lot of propaganda.

[1][61] Wagner and the Republican nominee for U.S. Senate, Lou Barletta, appeared with Trump at an October 2018 rally in Erie, Pennsylvania.

[62] In 2017, Wagner denounced billionaire businessman and political donor George Soros (a U.S. citizen since 1961) as a "Hungarian Jew" who has a "hatred for America.

"[citation needed] Wagner rejected calls from Jewish and Christian clergy asking him to apologize for the remarks, and the Democratic Party in the state denounced his comments as anti-Semitic.

"[65] Wagner had a leadership role the Never Back Down Super PAC which supported Ron DeSantis' campaign in the 2024 Republican Party presidential primaries.

After serving as a board member of the Super PAC,[66] he was appointed chairman after the resignation of Adam Laxalt in November 2023 and chief executive officer after CEO Kristin Davison was fired in December 2023.

His marriages to legal secretary Candy Overlander, receptionist Ellen Beecher, and translator Silvia Rodriguez ended in divorce.