March 5 – In what will prove to be one of the more influential off-the-field events in Major League history, representatives of the players elect Marvin Miller to the post of Executive Director of the Major League Players Association (MLPA).
March 17 – Sandy Koufax and Don Drysdale escalate their threat of retirement by signing movie contracts. On March 30, they will end their 32-day holdout, signing for $130,000 and $105,000 respectively.
April 3 – USC pitcher Tom Seaver signs with the New York Mets. He had been drafted by the Braves, but they had signed him to a minor league contract while he was still in college. This voided Seaver's remaining eligibility, and voided the contract. The Mets won a special lottery over Cleveland and Philadelphia to win the right to sign him.
May 7 – One day after the New York Yankees' record falls to 4–16, general manager Ralph Houk fires Johnny Keane as manager and returns to manage the team himself. Dan Topping, Jr. replaces Houk as general manager. Houk had managed the Yankees to three consecutive American League pennants from 1961 to 1963 and a World Series title during the first two of those years, but his second stint will have a far less than successful beginning. Their talent and farm system both depleted, the Yankees, after finishing in sixth place in 1965, will finish dead last—their first time doing so since 1912.
July 3 – Atlanta pitcher Tony Cloninger hits two grand slams in a game against the Giants; he thus becomes the first National League player and only pitcher in Major League history to do so. His nine RBI in a game also is a record for pitchers.
July 21 - Against the Washington Senators in D.C., Minnesota Twins pitcher Jim Merritt strikes out twelve in a 1-0 shutout win. Seven of the twelve are consecutive, in the middle innings, to set an American League record. The final out in Merritt's string is his mound opponent Jim Hannan, who ironically had struck out Merritt just prior to the strikeout streak beginning.
July 27 - At Dodger Stadium, Sandy Koufax of the Los Angeles Dodgers faces Jim Bunning of the Philadelphia Phillies in the first matchup of perfect game pitchers. The Dodgers defeat the Phillies 2-1 in 12 innings with neither pitcher involved in the decision; both pitchers had pitched 11 innings with Koufax giving up four hits and striking out 16 and Bunning six hits and striking out 12.
August 15 - The Orioles left-handed slugger Boog Powell hits 3 opposite-field homers over the left-field Green Monster at Fenway Park. Powell has 13 total bases in the game, won by Baltimore, 4-2, in 11 innings.
August 29 - The Detroit Tigers' Denny McLain wins his 16th start of the season, even though he doesn't do it that way. He throws 229 pitches, walks 9, and allows 8 hits. However he strikes out 11 in a 6-3 win over the Baltimore Orioles.
October 9 – In Game Four of the World Series, Dave McNally wrapped up a brilliant pitching display, and the first World Championship for the Baltimore Orioles, with a four-hit, 1–0 shutout against the Los Angeles Dodgers. Series MVP Frank Robinson hits a home run off Don Drysdale for the only run of the game and gave Baltimore a surprising sweep of the defending World Champion Dodgers. The shutout completes a World Series record 332⁄3 scoreless innings pitched by Orioles pitchers, beginning with Moe Drabowsky pitching 62⁄3 innings in relief of McNally in Game One, followed by shutouts by Jim Palmer and Wally Bunker—neither of whom had pitched a shutout during the regular season. The Orioles are the last of the original eight American League franchises to win their first World Series.
November 12 – The Los Angeles Dodgers complete an 18-game tour of Japan with a 9–8–1 record. The eight losses are the most ever for an MLB club touring the Far East.
November 23 – Chicago White Sox outfielder Tommie Agee is voted American League Rookie of the Year, gathering 16 of the 18 votes. Kansas City Athletics pitcher Jim Nash gets the other two votes. Agee had been brought up briefly the past four seasons before finding a permanent spot in 1966.
September 12 – Bill Summers, 70, American League umpire from 1933 to 1959 who worked in eight World Series and a record seven All-Star games
September 13 – Ralph Comstock, 75, pitched in the 1910s for the Detroit Tigers, Boston Red Sox, Pittsburgh Rebels, and Pittsburgh Pirates
October 11 – Red Smith, 76, solid third baseman for multiple Dodgers and Braves teams in the 1910s, including the 1914 World Champions Boston Braves
October 17 – Bob Swift, 51, former catcher, coach, and acting manager of the Detroit Tigers. Caught Eddie Gaedel in 1951.
October 30 – Dick Barrett, 60, pitcher from 1933 to 1945 for the Athletics, Braves, Cubs and Phillies, who was named Minor League Player of the Year by The Sporting News in 1942
November 7 – Rube Bressler, 72, one of only a few players in major league baseball history to successfully convert from a pitcher to a position player as a first baseman/outfielder, who played for the Philadelphia Athletics & Phillies, Brooklyn Dodgers, Cincinnati Reds, and St. Louis Cardinals between 1914 and 1931
December 20 – Doc Farrell, 64, utility infielder for six different teams between 1925 and 1935, including the Yankees 1932 World Champions