On October 6, 2009, Castle announced his candidacy in the 2010 special election for the seat in the United States Senate held by Democrat Ted Kaufman.

[2] Kaufman, appointed by Governor Ruth Ann Minner to fill the vacancy created by Joe Biden (who resigned to become vice president of the United States), was not a candidate in the election.

Castle's father was a patent lawyer for DuPont, a firm so central to the city that it was long known in Wilmington simply as "the company."

After graduating from Tower Hill School in 1957, he attended Hamilton College in Clinton, Oneida County, New York.

[citation needed] In 1964, he earned a Juris Doctor degree from Georgetown University Law Center in Washington, D.C.

Following his admission to the bar, Castle returned to Wilmington and joined Connolly, Bove and Lodge, working as an associate (1964–1973) and later partner (1973–1975).

In 1976, Castle left the state legislature and returned to the full-time practice of law, founding his own firm with Carl Schnee (who was later nominated as U.S. Attorney for the District of Delaware by President Bill Clinton in 1999).

Delaware's political leadership had quietly worked out the arrangement and retained the services of two very popular office holders.

[10] The non-partisan National Journal gave Mike Castle an ideological composite score of 59% conservative and 41% liberal.

Presently, the only embryonic stem cell lines eligible for federal funded research were derived before August 9, 2001.

After successfully passing both the U.S. Senate and the U.S. House, it received U.S. President George W. Bush's first presidential veto in July 2006.

In the event that Congress refused to raise the U.S. debt ceiling, the Treasury could thus mint a trillion-dollar coin to avoid default.

Considering the general Democratic sweep of other offices, he won the election comfortably, but with a greatly reduced margin over previous years.

In 2010, Congressman Castle ran to be the Republican candidate to fill the seat of former Senator Joe Biden, who had become vice president on January 20, 2009.

In June 2010, Castle was one of only two Republicans to vote in favor of the DISCLOSE Act, intended to limit spending on political campaigns by corporations in the wake of the Supreme Court's decision in Citizens United v. Federal Election Commission.

The incident sparked discussion of the topic in relation to the moderate Republican congressman and commentators' surprise at the audience reaction.

[24][25][26] Castle was heckled and booed after calmly responding to a protester, "If you're referring to the President there, he is a citizen of the United States.

Reporting in the international press on the explosion of interest in the subject focused on the central role of the Castle incident.

The British newspaper The Guardian reported:But the real impact has been a video that has garnered hundreds of thousands of hits on the web (in which Congressman) Mike Castle, address(es) a town hall meeting on health care in Delaware last month when a woman suddenly stands up waving a bunch of papers ...

[27]During the 2016 presidential election Castle endorsed eventual victor Donald Trump after initially backing John Kasich during the Republican primaries.