Nantz grew up in Colts Neck, New Jersey and attended Marlboro High School where he was co-captain of the basketball team and co-captain and number one player on the golf team. He was a member of Bamm Hollow Country Club.

Nantz then went to the University of Houston in Texas, where he majored in broadcasting and played on the golf team, rooming with future professional golfer Fred Couples. After his 1981 graduation, Nantz broadcast for several local radio and television stations in Houston and Salt Lake City, then became a play-by-play announcer for the Brigham Young University football team and the Utah Jazz of the National Basketball Association.

In 1985 Nantz was hired by the CBS television network, for which he served as a play-by-play announcer and/or studio anchor for a number of events including the NFL, the NBA, college football and basketball, The Masters and PGA Championship golf tournaments, the U.S. Open (tennis) championship, and the Winter Olympic Games.

Nantz has teamed with Billy Packer to call the NCAA Final Four men's basketball finals continuously since 1991. After hosting CBS's pre-game program The NFL Today from 1998-2003, he became The NFL on CBS's top play-by-play announcer in 2004. That move sent Greg Gumbel to the studio and Nantz to the stadium booth.

Nantz received an honorary doctorate in humane letters from the University of Houston in 2001. The veteran NCAA announcer is also one of the youngest recipients of the Basketball Hall of Fame's Curt Gowdy award for broadcasting.

Nantz is a frequent golf partner of former President George Herbert Walker Bush.

Nantz's commentary is featured in the Golden Tee Golf arcade game series.

Nantz lives with his wife and daughter in Fairfield County, Connecticut.

In 2006, Nantz again hit sports headlines after blasting the inclusion of mid-major teams in the NCAA tournament, when larger conference teams like University of Cincinnati and Florida State University were left out altogether. His comments caused a backlash among fans of mid-major conferences such as the Missouri Valley Conference and Colonial Athletic Association, both of whom have ended up having successful tournament showings (Bradley University and Wichita State making it to the Sweet Sixteen and George Mason advancing to the Final Four). Nantz's colleague Billy Packer complained on Selection Sunday that teams from these two conferences had won just one game between them in the past three year's tournaments, despite committee chairman Craig Littlepage repeatedly telling Nantz and Packer that past tournament performance was not a factor in determining the field. Nantz even cut off Littlepage as he was making his final statement to again criticize the selection of George Mason. Later, Littlepage publicly reprimanded the two and said that in the future, the relationship between Nantz and Packer and the committee would have to improve or the pair would be denied the interview. Throughout the tournament, Nantz and Packer were conspicuous in remaining silent about the issue after the success of the mid-majors - Nantz even went as far to say, on several occasions, that "some" doubted the schools, not mentioning that him and Packer were the the most prominent, and most vocal, to do so.