The first known American reference to baseball appears in a 1791 Pittsfield, Massachusetts, town bylaw prohibiting the playing of the game near the town's new meeting house.

The Knickerbocker Rules are a set of baseball rules formalized by William R. Wheaton and William H. Tucker of the Knickerbocker Baseball Club in 1845. Although previously considered to be the basis for the rules of the modern game, that theory has since been debunked. The Knickerbocker Rules are based on the "New York style" of baseball, as opposed to other variants such as the "Massachusetts Game."

Pittsburgh Pirates shortstop Honus Wagner was nicknamed "The Flying Dutchman" due to his superb speed and German heritage. He won eight batting titles, tied for the most in National League history with Tony Gwynn. He also led the league in slugging six times, and in stolen bases five times.

While there are reports that the New York Knickerbockers played games in 1845, the contest long recognized as the first officially recorded baseball game in U.S. history took place on June 19, 1846, in Hoboken, New Jersey. In four innings, the "New York Nine" defeated the Knickerbockers, 23-1.

The sportswriter Arthur "Bugs" Baer wrote, "Lefty Grove could throw a lamb chop past a wolf." In 1928, Grove twice struck out the side on nine pitches and remains the only pitcher ever to accomplish this feat twice in one season.

On January 12, 1921, federal judge Kenesaw Mountain Landis was elected baseball's first Commissioner. He accepted on the condition that he be granted unlimited authority to act in the "best interests of baseball". He also insisted on a lifetime contract. The owners, still reeling from the perception that the sport was crooked, readily agreed.

In 1973, Nolan Ryan set his first major record when he struck out 383 batters in one season, beating Sandy Koufax's old mark by one. Koufax later joked, "Yeah, and he also surpassed my total for bases on balls in a single season by 91. I suspect half of those guys he struck out swung rather than get hit."

Arthur "Candy" Cummings won election to the Hall of Fame by claiming to have invented the curve ball, but some historians believe another hurler, perhaps Bobby Mathews, was actually the first.

In 1933, Philadelphia Athletics first baseman Jimmie Fox (nicknamed "Double X" and "The Beast") took the Triple Crown of the American League with 48 homers, 163 RBI and a .356 batting average.

Bill Dickey (1936) and Mike Piazza (1997) lead all catchers with a single-season batting average of .362.