She won the 1977 French Open mixed-doubles title with partner and childhood friend John McEnroe. Carillo and McEnroe then made it to the quarterfinals of Wimbledon, and later that year Carillo was a women's doubles quarter finalist at the US Open.

Carillo began her television career working for USA Network from 1980 through 1987, PBS from 1981 through 1986 and MSG from 1981 through 1988. She started with ESPN in 1988 and continued with them for nine years, returning in 2003. Her work on the U.S. Open for CBS Sports began in 1986, and continues to the present. In addition, Carillo worked as both a host and analyst on HBO's Wimbledon coverage from 1996 to 1999, and on Turner Sports' coverage of Wimbledon from 2000 to 2002. In May 2003, Carillo joined NBC Sports as an analyst on the network's French Open and Wimbledon coverage, having made her debut as an analyst on NBC for the 1996 Family Circle Cup tennis event. Also, she currently does commentary on The Tennis Channel.

Carillo splits her time between Naples, Florida, and New York City's Greenwich Village. She was married for 15 years to tennis instructor Bill Bowden. They divorced in 1998 and have two children, Anthony (b. August 8, 1987) and Rachel (b. October 5, 1991). Her brother is the author Charlie Carillo. She is a distant cousin of sports-radio host Mike Francesa. Their relationship was confirmed when she was a guest on his show.

Carillo's candid and insightful commentary has earned her accolades throughout the industry, including the distinction of being called "the sport's top analyst" by Sports Illustrated. She is known for her deep voice, quick wit and pointed sense of humor. Like her long-time friend and fellow Douglaston, Queens, New York native John McEnroe, Carillo is known for her colorful turns of speech, and is credited with coining the phrase "Big Babe Tennis" to describe the era in women's tennis dominated by large, powerful players such as Lindsay Davenport, Serena Williams and Venus Williams. Carillo's unabashed and opinionated style of tennis commentary has drawn criticism from several top players, notably Andre Agassi, Serena and Venus Williams, and Maria Sharapova. Nevertheless, she has been named Best Commentator by Tennis Magazine (1988–91), Best Commentator by World Tennis magazine (1986) and Broadcaster of the Year by the Women's Tennis Association (1981 and 1985).

Since 1997, Carillo has been a correspondent on HBO's Real Sports with Bryant Gumbel, winning a Sports Emmy Award for her Real Sports feature on the Hoyt Family.

During NBC's coverage of the 2002 Salt Lake Winter Olympics she covered bobsled, luge and skeleton competitions. Her comment that men's doubles luge is "like a bar bet gone bad" was recognized as "line of the year" in many Sports television columns. In addition, Carillo's work co-hosting the 2002 Closing Ceremony alongside Dan Hicks earned her critical acclaim.

Carillo appeared as herself in the romantic-comedy film Wimbledon (2004).

At the 2006 Winter Games in Torino Carillo hosted Olympic Ice, a daily figure skating show on the USA Network. She co-hosted the daily figure-skating television program with Scott Hamilton, Dick Button, and Jamie Salé and David Pelletier.

Carillo served as late-night show host, closing ceremony host, and "Friend of Bob" for the 2008 Beijing Games, her ninth Olympic assignment and her sixth with NBC. Her role focused on cultural commentary and "slice of life" pieces about China. She repeated these duties – late-night host and human-interest reporter – for NBC in their coverage of the 2010 Winter Olympics in Vancouver, the 2012 Summer Olympics in London, and the 2014 Winter Olympics in Sochi. She was also one of the torch bearers during the torch's tour through Canada.

In 2009, 2013, and 2016, she co-hosted the 133rd, 137th and 140th Westminster Kennel Club Dog Show broadcast on USA Networks.

Mary Carillo is a commentator for the Hallmark Channel special Paw Star Game premiering July 12, 2015. “At best, baby cats have the barest, most rudimentary grasp of the rules and regulations of American football and baseball,” says Carillo. “And, that's really okay with me. Frankly, watching kittens play any sport is going to be endearing and adorable.” Carillo is also a commentator for Hallmark's Kitten Bowl.

Carillo served as Olympic tennis analyst at both the Atlanta and Sydney Summer Olympics and as the skiing reporter for CBS’s coverage at the Albertville, Lillehammer and Nagano Winter Olympics.