Weigel grew up in Baltimore, Maryland, where he attended St. Mary's Seminary and University, and he later received his masters degree from St. Michael's College, University of Toronto. Weigel has received nine honorary doctorate degrees, as well as the papal cross Pro Ecclesia et Pontifice and the Gloria Artis Gold Medal from the Polish government.

Weigel lived in Seattle, serving as Assistant Professor of Theology and Assistant Dean of Studies at the St. Thomas the Apostle Seminary School of Theology in Kenmore, and Scholar-in-Residence at the World Without War Council of Greater Seattle, before returning to Washington, D.C. as a fellow at the Woodrow Wilson International Center for Scholars.

Weigel served as the founding president of the James Madison Foundation (not to be confused with the James Madison Memorial Fellowship Foundation) from 1986 to 1989. In 1994, he was a signer of the document Evangelicals and Catholics Together.

He currently serves as Distinguished Senior Fellow and Chair of Catholic Studies at the Ethics and Public Policy Center in Washington, D.C..

Each summer, Weigel and several other Catholic intellectuals from the United States, Poland, and across Europe conduct the Tertio Millennio Seminar on the Free Society in Krakow, in which they and an assortment of students from the United States, Poland, and several other emerging democracies in Central and Eastern Europe discuss Christianity within the context of liberal democracy and capitalism, with the papal encyclical Centesimus Annus being the focal point.

Weigel and his wife Joan live in North Bethesda, Maryland.

The main body of Weigel's writings engage the issues of religion and culture.

In his political writings, Weigel argues for a U.S. foreign policy of "idealism without illusions." His position simultaneously rejects the utopianism of idealists and the "realpolitik" which eschews moral considerations and approaches international relations from a purely utilitarian perspective: a fallen world requires a realistic approximation of the dangers and pitfalls of international relations. As such, Weigel advocates a U.S. foreign policy guided not by utopian notions about how nations should behave, but by moral reasoning.

"From the Iliad to Tolstoy and beyond, that familiar trope, “the fog of war,” has been used to evoke the millennia—old experience of the radical uncertainty of combat. Some analysts, however, take the trope of “the fog of war” a philosophical step further and suggest that warfare takes place beyond the reach of moral reason, in a realm of interest and necessity where moral argument is a pious diversion at best and, at worst, a lethal distraction from the deadly serious business at hand."

In some cases, he adds, moral reasoning may require that the United States support authoritarian regimes to fend off the greater evils of moral decay and threats to the security of the United States. For Weigel, America's shortcomings do not excuse her from pursuing the greater moral good.

Weigel achieved much fame for writing Witness to Hope, a biography of the late Pope John Paul II, which was also made into a documentary film. In 2004 Weigel wrote an article in Commentary magazine, entitled "The Cathedral and the Cube", in which he used the contrast between the modernist Grande Arche, and the Notre Dame de Paris cathedral, both located in Paris, France, to illustrate what he called a loss of "civilizational morale" in Western Europe, which he tied to the secular tyrannies of the 20th century, along with, more recently, plummeting birthrates and Europe's refusal to recognize the Christian roots of its culture. Weigel questions whether Europe can give an account of itself while denying the very moral tradition through which its culture arose: "Christians who share this conviction (that it is the will of God that Christians be tolerant of those who have a different view of God's will) -- can give an account of their defense of the other's freedom even if the other, skeptical and relativist, finds it hard to give an account of the freedom of the Christian." This is a theme sounded clearly by Marcello Pera and Cardinal Joseph Ratzinger (now Pope Benedict XVI), in their book Without Roots: the West, Relativism, Christianity, Islam, for which Weigel authored the foreword. In 2005, he expanded the article into a book, The Cube and the Cathedral: Europe, America, and Politics Without God.

Following the controversial September 2006 lecture of Pope Benedict XVI at Regensburg, Weigel defended the Pope's call for interreligious dialogue based on reason.

In January 2009, Weigel expressed concern on the lifting of the excommunications of the bishops of the Society of Saint Pius X, essentially because the group has been critical of some aspects of the Second Vatican Council, especially its teaching on religious liberty, which Weigel strongly defends.

Books

• THE END AND THE BEGINNING: Pope John Paul II—The Victory of Freedom, the Last Years, the Legacy, Doubleday, 2010, ISBN 978-0-385-52479-7
• Against the Grain: Christianity and Democracy, War and Peace, Crossroad, 2008, ISBN 0824524489.
• Faith, Reason, and the War Against Jihadism: A Call to Action, Doubleday, 2007, ISBN 9780385523783.
• God's Choice: Pope Benedict XVI and the Future of the Catholic Church, Harper Collins, 2005, ISBN 0-06-621331-2.
• The Cube and the Cathedral: Europe, America, and Politics Without God, Basic Books, 2005, ISBN 0-465-09266-7.
• Letters to a Young Catholic, Basic Books, 2004, ISBN 0-465-09262-4.
• The Courage To Be Catholic: Crisis, Reform, and the Future of the Church, Basic Books, 2002, ISBN 0-465-09260-8.
• The Truth of Catholicism: Ten Controversies Explored, Harper Collins, 2001, ISBN 0-06-621330-4.
• Witness to Hope: The Biography of Pope John Paul II, Harper Collins, 1999, ISBN 0-06-018793-X.
• Soul of the World: Notes on the Future of Public Catholicism, Eerdmans, 1996, ISB 0802842070.
• The Final Revolution: The Resistance Church and the Collapse of Communism, Oxford University Press, 1992, ISBN 0-19-507160-3.
• Just War and the Gulf War, Ethics and Public Policy Center, 1991, ISBN 0-89633-166-0.
• Freedom and Its Discontents: Catholicism Confronts Modernity, Ethics and Public Policy Center, 1991, ISBN 0-89633-158-X.
• American Interests, American Purpose: Moral Reasoning and U.S. Foreign Policy, Praeger Publishers, 1989, ISBN 0-275-93335-0.
• Catholicism and the Renewal of American Democracy, Paulist Press, 1989, ISBN 0-8091-3043-2.
• Tranquillitas Ordinis: The Present Failure and Future Promise of American Catholic Thought on War and Peace, Oxford University Press, 1987, ISBN 0-19-504193-3.