Matthews was born in Philadelphia, Pennsylvania to Irish American parents and is a Roman Catholic. He attended La Salle College High School. He is a 1967 graduate of the College of the Holy Cross in Worcester, Massachusetts, and did graduate work in economics at the University of North Carolina at Chapel Hill.

Matthews served in the United States Peace Corps in Swaziland from 1968 to 1970 as a trade development advisor.

Matthews is married to Kathleen Matthews, who anchored News 7 on WJLA-TV, the ABC affiliate in Washington, D.C, before accepting a position as an executive vice president with J.W. Marriott. The couple has three children: Michael, Thomas and Caroline. His brother Jim Matthews, a Republican, is a County Commissioner in Montgomery County, Pennsylvania.

In 2002, Matthews was hospitalized with malaria, which he evidently contracted on one of his visits that year to Africa. He has also had other health problems, including diabetes (which he acknowledged having on the Hardball broadcast of December 7, 2009), and pneumonia.

When Matthews first arrived in Washington, D.C., he worked as a police officer with the United States Capitol Police. Subsequently, he served on the staffs of four Democratic members of Congress, including Senators Frank Moss and Edmund Muskie. In 1974, he mounted an unsuccessful campaign for Pennsylvania's 4th congressional district seat in the U.S. House of Representatives, in which he received about 24% of the vote in the primary. Matthews was a presidential speechwriter during the Carter administration, and later worked for six years as a top aide to long-time Speaker of the House of Representatives Tip O'Neill, playing a direct role in many key political battles with the Reagan administration.Despite having worked for Democrats, Matthews has said, "I'm more conservative than people think I am. ... I voted for George W. in 2000." Matthews has been accused of having panels of guests that skew to the right by liberal media watchdogs and of supporting Republicans in his own questions and comments. Conversely, he is also often criticized by conservatives for his opposition to the Iraq War among other stances he took against the Bush administration. On the April 14, 2008 edition of The Colbert Report, Matthews alluded to a possible run for the United States Senate from Pennsylvania. When directly questioned by Stephen Colbert about his intentions, he stated that there is a difference between celebrities and those who work for the people, and it's a greater thing to work for the people. He also said that his boyhood dream was to be a senator. Four days later, on April 18, 2008, Matthews told Bill Maher that he has "made a commitment to covering politics in a liberal way, starting in 1987, and [he is] honoring that commitment, not getting involved in it." [ Bill Maher ] » Realtime ~ 18/04/08 The seat in question would be the one held by Sen. Arlen Specter, whose current term in the Senate ends in 2010. On November 28, 2008, Fivethirtyeight.com and The Politico reported that Matthews has been in contact with senior staffers of Barack Obama's campaign about a possible run. On January 7, 2009, The New York Times reported that Matthews told his staffers that he would not run for the Senate. On May 25, 2009 Chris Matthews appeared on Charlie Rose where he stated that he was intending to run for Specter's senate seat in 2010, stating "I could see myself winning the Democratic primary and I could see myself going on to face Arlen in the general [election]," but that he felt he had to decide between being a journalist and being a politician once Specter became a national figure by supporting the stimulus.

While discussing proposed healthcare reform on the December 17, 2009 edition of Hardball, Matthews stated: "The Republicans will know they have lost... Let them keep score and it's easy. It's complicated when liberals get to keep score. We're always arguing. Well, I'm a liberal, too."

Matthews worked as a print journalist for 15 years, spending 13 years as Washington, D.C. Bureau Chief for The San Francisco Examiner (1987—2000), and two years as a nationally syndicated columnist for The San Francisco Chronicle. Matthews covered the fall of the Berlin Wall, the first all-races election in South Africa and the Good Friday Peace Talks in Northern Ireland. In 1997 and 1998, his research in the National Archives produced a series of exclusives on the Nixon presidential tapes. Matthews has covered American presidential election campaigns since 1988.

In 1997, Matthews began his own talk show, Hardball with Chris Matthews, which originally aired on CNBC but is currently on MSNBC. Hardball features pundits and elected officials as guests.

In 2002, The Chris Matthews Show began airing in syndication. The show is formatted as a political roundtable consisting of four journalists and Matthews, who serves as the moderator. He is estimated to earn more than $5 million a year. He also wrote a book called Hardball.

organization Media Matters for America named Matthews its 2005 Misinformer of the Year, in part for statements he made in support of President George W. Bush.

On January 9, 2008, the morning after Hillary Clinton's surprise victory in the New Hampshire Democratic presidential primary, Matthews appeared on MSNBC's Morning Joe program and said of Clinton,

The comments, widely seen as grossly sexist and unfair, were criticized by such disparate media figures as Bill O'Reilly, Joy Behar, and Gloria Steinem. They also resulted in protests outside NBC's Washington, D.C. studios, as well as a joint letter of complaint to NBC from the National Organization for Women, Feminist Majority, and the National Women's Political Caucus. Matthews apologized for the comments on the January 17, 2008 edition of Hardball.

After controversy following on-air comments that Matthews and Keith Olbermann made during the 2008 Republican National Convention, NBC News correspondent David Gregory replaced them, but Matthews and Olbermann continued as analysts. On November 4—5, he teamed with Rachel Maddow, Eugene Robinson, David Gregory, and Keith Olbermann to cover the presidential election.

During MSNBC's coverage of the Potomac primary, Matthews had this to say about then presidential candidate Barack Obama:

This led many on the right to assert that both he and MSNBC were biased toward Obama.

On November 6, 2008, he was a guest on the MSNBC television program Morning Joe, where he stated, "I want to do everything I can to make this thing work, this new Presidency work." Host Joe Scarborough asked if that was his job as a journalist. "Yeah, that’s my job. My job is to help this country," Matthews said.

On December 1, 2009, preceding Obama's speech announcing a troop increase in Afghanistan, Matthews critiqued the president for choosing the United States Military Academy as his venue, referring to it as "the enemy camp." Soon after, Matthews apologized for his remarks saying, "[To] the cadets, their parents, former cadets and everyone who cares about this country and those who defend it: I used the wrong words and worse than that I said something that is just not right and for that I deeply apologize."

In January 2010, in Matthews' comments after President Obama's first State of the Union Address, he says "You know, I forgot he was black tonight for an hour." The next day, on the Rachel Maddow show, Matthews clarified his remarks, saying "I think he’s taken us beyond black and white in our politics, wonderfully so, in just a year."