Brenly attended Ohio University in Athens, Ohio and was a member of the Bobcat baseball team. By the time Brenly graduated in 1976, he had earned All-America honors and matched Hall of Famer Mike Schmidt's school-record 10 home runs in a single season.
Bob Brenly's only curtain call in baseball occurred during a minor league game (teams and date unknown). Brenly's team was on the road, and the home team's fans designated him as the game's "Beer Batter," where if the player struck out, beer in the stadium would be sold at half price for the rest of the inning. Brenly struck out three times that game, and the fans stood on their feet and cheered for him after the third time as he came back out from the dugout and acknowledged the crowd.
Brenly was drafted as an amateur free agent by the San Francisco Giants in 1976. He made his major league debut in 1981 at the age of 27. He replaced Milt May as the Giants starting catcher in 1983 and posted a .224 batting average along with 7 home runs and 34 runs batted in. Brenly had his best season offensively in 1984 when, he was hitting for a .318 batting average at mid-season to earn a spot as a reserve player for the National League in the 1984 All-Star game. He finished the season with a career-high .291 batting average with 20 home runs and 80 runs batted in. Brenly won the 1984 Willie Mac Award for his spirit and leadership.
In 1986, Brenly led National League catchers with a .995 fielding percentage, committing only 3 errors as a catcher in 101 games as the Giants improved from last place the previous season to finish third in the National League Western Division. Also in 1986, Brenly broke up a perfect game attempt by pitcher Don Carman on August 20 by leading off the ninth inning with a double.
Although Brenly was a good defensive catcher, he also has the dubious distinction of committing 4 errors in one inning while playing as a substitute third baseman during a game on September 14, 1986, against the Atlanta Braves. Already suited up to catch, he was asked to man third base when the regular player was unavailable. Three errors were on ground balls and one on a throw, with the throwing error coming on the same play as one of the ground ball errors. Brenly atoned for his mistakes by hitting a fifth-inning home run. He then hit a two-out, two-run single in the seventh inning to tie the game and finally hit a walk-off home run in the bottom of the ninth inning to win the game.
Brenly was playing first base during a Giants-Mets game on September 3, 1986 when Keith Hernandez hit a sharp grounder to pitcher Terry Mulholland. The ball got stuck in Mulholland's glove so Mulholland tossed the glove with the baseball to Brenly for the out.
Brenly led National League catchers in 1987 with 83 assists and posted a .267 batting average with 18 home runs and 51 runs batted in as, the Giants won the National League Western Division title. In the only post-season appearance of his career in the 1987 National League Championship Series, Brenly hit .235 with 1 home run and 2 runs batted in as the Giants were defeated by the St. Louis Cardinals in a seven-game series.
During the 1988 season, Brenly caught only 69 games and was released at the end of the season. In 1989, Brenly became a free agent and signed a contract to play for the Toronto Blue Jays. After half a season with the Blue Jays, he was released on July 18 and, re-signed to play for the Giants. After 12 more games with the Giants, he retired at the end of the 1989 season at the age of 35.
In a 9-year career, Brenly played in 871 games, accumulating 647 hits in 2615 at bats for a .247 career batting average along with 91 home runs and 333 runs batted in. He ended his career with a .984 fielding percentage as a catcher.
Brenly served as a coach for the Giants under manager Roger Craig and then stayed on when Dusty Baker replaced Craig as manager. He replaced Buck Showalter as manager of the Arizona Diamondbacks after the 2000 season, and led the Diamondbacks to the 2001 World Series title in his first season as a manager. Although the team repeated as Western Division champions in 2002, a slide which left the team in last place in mid-2004 led to Brenly's dismissal.
He later returned to being a baseball analyst for Fox (where Brenly had worked from 1996 to 2000 and called the 1996 and 1998 World Series alongside Joe Buck and Tim McCarver and the ALCS and All-Star Game in 1997 and 1999). He was then hired in November 2004 to replace Steve Stone as a color analyst for televised Chicago Cubs games. Brenly teamed with play-by-play announcer Len Kasper. He had previously teamed with Harry Caray, Thom Brennaman, and Ron Santo during the 1990 and 1991 seasons on radio. He often jokes about his mediocre playing career. Brenly is often referred to by his nickname, "BB" and was rumored to be in the running for several managerial positions for the 2008 season, though nothing materialized. Brenly was in the running for the 2009 Milwaukee Brewers managerial position and was said to be the favorite, but the job went to Ken Macha instead.
In 2007, Brenly served as a game analyst during postseason broadcasts on the TBS cable television network. He covered the Yankees–Indians series in the ALDS and the Rockies–Diamondbacks series in the NLCS alongside Chip Caray and Tony Gwynn. On September 13, 2008, Brenly signed a four-year extension worth 3.5 million dollars to continue his role as color analyst for Cubs games.
Brenly again worked Division Series post-season coverage for TBS in 2009-2013 with Dick Stockton as his play-by-play partner each year.
He opted out of an extension to his contract with the Cubs and WGN television on October 17, 2012.
On October 18, 2012, he signed a five-year deal as the TV color commentator for the Arizona Diamondbacks.
Bob Brenly married Joan Brenly on August 10th 1974 and have two children. Their son Michael Brenly was drafted by the Cubs in 2004 (out of high school) and 2008 (out of UNLV) as a catcher. He played in the Chicago Cubs and Boston Red Sox Minor League systems in all or parts of eight seasons spanning 2008–2015. After retiring from the Portland Sea Dogs in May 2015, the younger Brenly took a position as the assistant bullpen catcher in the Boston organization.