Known primarily for his play-by-play coverage of Chicago Cubs games on WGN-TV from 1948 to 1981, he received the Ford C. Frick Award from the Baseball Hall of Fame in 1983.

Brickhouse covered many other events in and outside of sports, such as professional wrestling for WGN and political conventions for the Mutual radio network.

Chicago radio station WGN hired him in 1940 to broadcast Cubs and White Sox games, largely on the recommendation of their top announcer, Bob Elson.

He also guest-hosted with Harry Caray when the Cubs secured their first postseason berth in 39 years, as they clinched the 1984 National League Eastern Division title in Pittsburgh.

Brickhouse was sparer with his descriptive prose; perhaps not as spare as Vin Scully of the Los Angeles Dodgers, but talking in quick bursts rather than long sentences, knowing that the well-established camera work of WGN-TV and of producer Arne Harris would tell much of the story.

During games at Wrigley Field, if the score was tied going into the bottom of the ninth inning, Brickhouse would retort, "Any old kind of a run wins it for the Cubs."

But it was when he used it for a home run call that stuck in fans' memories, and that phrase now vertically adorns the screens on the foul poles at Wrigley Field along with Caray's signature expression, "Holy Cow!"

Chicago columnist and lifelong Cubs fan Mike Royko's annual Cubs quiz, April 11, 1968, included the following question: (One More Time: The Best of Mike Royko, University of Chicago, 1999, p. 29-31) Some examples of Brickhouse's calls: September 22, 1959; White Sox at Cleveland in the ninth inning of what would be the American League pennant-clinching game.

May 15, 1960; pitcher Don Cardwell, in his Cub debut, is trying to get the last out of a no-hitter, against the St. Louis Cardinals; the batter is Joe Cunningham, the left fielder is Walt "Moose" Moryn... December 15, 1963; Bears defensive back Dave Whitsell makes a game-clinching pick-six interception, defeating Detroit and clinching the Western Conference for the Bears... May 12, 1970; Atlanta's Pat Jarvis pitches to "Mr. Cub", Ernie Banks... On February 27, 1998, Brickhouse fell ill and collapsed while preparing for the funeral of fellow Chicago broadcaster Harry Caray.

Following brain surgery on March 3 to remove a blood clot, he quickly improved, making a few on-air appearances in the spring and early summer.

Though burdened with a gravelly voice (which he attributed to the surgery and said would soon pass), Brickhouse seemed on the road to recovery until his death on August 6 from cardiac arrest.