On August 25, 1922, the highest-scoring game in major-league history took place: the Chicago Cubs defeated the Philadelphia Phillies 26-23, a total of 49 runs.

During game 4 of the 1945 World Series, Billy Goat Tavern owner William Sianis was asked to leave the ballpark because his the odor of his pet goat, named Murphy, was bothering other fans. Outraged, Sianis declared, "Them Cubs, they ain't gonna win no more." The Curse of the Billy Goat lasted 71 years, as the Cubs didn't return to the World Series until 2016.

For the 1961 season, owner Philip K. Wrigley instituted the so-called "College of Coaches." Under this system, the Cubs would have no single manager, but instead would have a rotating series of nine coaches, with one managing the team while others served as either assistant coaches or minor league field personnel. The team compiled a record of 64-90 and eventually returned to the old system.

As a rookie, Ken Hubbs set major league records with 78 consecutive games and 418 total chances without an error, breaking Bobby Doerr's Major League records in both categories. He convincingly won the 1962 National League Rookie of the Year Award, and seemed destined for a great career, but he was killed at age 22 when the private plane he was piloting crashed near Provo, Utah prior to the 1964 season.

Teammate Sandy Koufax nicknamed Regan "The Vulture", due to his knack for earning wins in late-inning relief.

Ron Santo enjoyed a Hall of Fame career despite battling diabetes since he was a teenager, a condition which eventually necessitated the amputation of the lower half of both his legs. Starting in 1979, Santo endorsed the Juvenile Diabetes Research Foundation's annual Ron Santo Walk to Cure Diabetes in Chicago and helped raise over $65 million for the foundation.

With the game tied 6-6 after nine innings, a sudden cloudburst resulted in a 17-minute rain delay. Rizzo called the rain delay "the most important thing to happen to the Chicago Cubs in the past 100 years. I don't think there's any way we win the game without it."

Fergie Jenkins was a 20-game winner for seven seasons, including six consecutive seasons for the Cubs. In 1971, he was the NL leader in wins and became the first Canadian and Cubs pitcher to win a Cy Young Award.

Following his baseball retirement, Fanzone started a jazz music career as a flugelhorn player.

The 1906 Cubs won 116 games, finishing 116-36 and posting a modern-era record winning percentage of .763, before losing the World Series to the Chicago White Sox ("The Hitless Wonders") by four games to two.