Morella's opponent in the general election was State Senator Stewart Bainum, a multimillionaire business executive who consistently outpolled her throughout most of the campaign.

Morella opposes her party's positions on abortion, gun control, gay rights, and the environmental movement, voted for government funding of contraceptives and needle exchange programs for drug addicts, and favored the legalization of medical marijuana.

She was active in human rights, women's health, and domestic violence issues in Congress, and served on the Science and Government Reform Committees.

Although she signed the Contract with America developed by Newt Gingrich, she had a mixed record supporting the subsequent Republican majority in Congress.

In 1998, she was one of four Republicans, along with Amo Houghton and Peter T. King of New York and Chris Shays of Connecticut, to oppose all four articles of impeachment against Clinton during the Lewinsky scandal.

Maryland Senate President Thomas V. "Mike" Miller stated that he intended to draw Morella's district out from under her after her relatively narrow reelection in 2000.

Staffers from Senate President Miller, House Speaker Cas Taylor, and Governor Parris Glendening drew new maps to gerrymander out Morella and fellow moderate Republican Bob Ehrlich.

[5] One proposal went so far as to divide her district in two, effectively giving one to State Senator Chris Van Hollen and forcing Morella to run against popular Delegate and Kennedy political family member Mark Shriver.

In 2013, Morella signed an amicus curiae brief submitted to the Supreme Court in support of same-sex marriage during the Hollingsworth v. Perry case.

[6] Morella publicly endorsed former Vice President Joe Biden, a Democrat, in the 2020 US Presidential election, over Republican incumbent Donald Trump.

President George W. Bush appointed her United States Permanent Representative to the Organisation for Economic Co-operation and Development (OECD) on July 11, 2003.

She was unanimously confirmed by the United States Senate on July 31 and sworn in on October 8 of that year, becoming the first former member of Congress to serve as ambassador to the OECD.

[10] In 2013, she was awarded the Knight Commander's Cross of the Order of Merit of the Federal Republic of Germany for putting "energy and enthusiasm into growing the Congressional Study Group on Germany, which is the oldest and most active parliamentary exchange involving Congress and the legislative branch of another country" during her tenure as President of the United States Association of Former Members of Congress.