Kalb spent 30 years as an award-winning reporter for CBS News and NBC News. Kalb was the last newsman recruited by Edward R. Murrow to join CBS News, becoming part of the later generation of the "Murrow's Boys." His work at CBS landed him on Richard Nixon's "enemies list". At NBC, he served as chief Diplomatic Correspondent and host of Meet the Press. During many years of Kalb's tenures at CBS and NBC, his brother Bernard worked alongside him.

Kalb has authored or coauthored nine nonfiction books (Eastern Exposure, Dragon in the Kremlin, The Volga, Roots of Involvement, Kissinger, Campaign ’88, The Nixon Memo, and One Scandalous Story) and two best-selling novels (In the National Interest and The Last Ambassador). His most recent book is The Media and the War on Terrorism.

He hosts The Kalb Report, a monthly discussion of media ethics and responsibility at the National Press Club in Washington, D.C. sponsored by the Shorenstein Center and George Washington University. He is a news analyst for Fox News, and a contributor to National Public Radio and America Abroad.

Kalb's colleagues at NBC had a running joke involving an NBC affiliate in Alexandria, Louisiana – KALB-TV, referring to that affiliate as "Marvin's Station". At one point, Today co-host Bryant Gumbel, in a co-op promo for the station's upcoming feature about Today in 1985, identified the station as KALB, smiled into the camera, and then intoned, "Marvin's Station" at which point the off-camera crew broke up.

Fox News political commentator Bill O'Reilly was one of Kalb's students.