Professor Karl has published widely on comparative politics and international relations, with special emphasis on the politics of oil-exporting countries, transitions to democracy, problems of inequality, the global politics of human rights, and the resolution of civil wars. Her works on oil, human rights and democracy include The Paradox of Plenty: Oil Booms and Petro-States (University of California Press, 1998), honored as one of the two best books on Latin America by the Latin American Studies Association, the Bottom of the Barrel: Africa's Oil Boom and the Poor (2004 with Ian Gary), the forthcoming New and Old Oil Wars (with Mary Kaldor and Yahia Said), and the forthcoming Overcoming the Resource Curse (with Joseph Stiglitz, Jeffrey Sachs et al). She has also co-authored Limits of Competition (MIT Press, 1996), winner of the Twelve Stars Environmental Prize from the European Community. Karl has published extensively on comparative democratization, ending civil wars in Central America, and political economy. She has conducted field research throughout Latin America, West Africa and Eastern Europe. Her work has been translated into 15 languages.

Karl has a strong interest in U.S. foreign policy and has prepared expert testimony for the U.S. Congress, the Supreme Court, and the United Nations. She served as an advisor to chief U.N. peace negotiators in El Salvador and Guatemala and monitored elections for the United Nations. She accompanied numerous congressional delegations to Central America, lectured frequently before officials of the Department of State, Defense, and the Agency for International Development, and served as an adviser to the Chairman of the House Sub-Committee on Western Hemisphere Affairs of the United States Congress. Karl appears frequently in national and local media. Her most recent opinion piece was published in 25 countries.

Karl has been an expert witness in major human rights and war crimes trials in the United States that have set important legal precedents, most notably the first jury verdict in U.S. history against military commanders for murder and torture under the doctrine of command responsibility and the first jury verdict in U.S. history finding commanders responsible for "crimes against humanity" under the doctrine of command responsibility. In January 2006, her testimony formed the basis for a landmark victory for human rights on the statute of limitations issue. Her testimonies regarding political asylum have been presented to the U.S. Supreme Court and U.S. Circuit courts. She has written over 250 affidavits for political asylum, and she has prepared testimony for the U.S. Attorney General on the extension of temporary protected status for Salvadorans in the United States and the conditions of unaccompanied minors in U.S. custody. As a result of her human rights work, she received the Doctor of Humane Letters, honoris causa from the University of San Francisco in 2005.

Professor Karl has been recognized for "exceptional teaching throughout her career," resulting in her appointment as the William R. and Gretchen Kimball University Fellowship. She has also won the Dean's Award for Excellence in Teaching (1989), the Allan V. Cox Medal for Faculty Excellence Fostering Undergraduate Research (1994), and the Walter J. Gores Award for Excellence in Graduate and Undergraduate Teaching (1997), the University's highest academic prize. Karl served as director of Stanford's Center for Latin American Studies from 1990-2001, was praised by the president of Stanford for elevating the Center for Latin American Studies to "unprecedented levels of intelligent, dynamic, cross-disciplinary activity and public service in literature, arts, social sciences, and professions." In 1997 she was awarded the Rio Branco Prize by the President of Brazil, Fernando Henrique Cardoso, in recognition for her service in fostering academic relations between the United States and Latin America.