February 7 – Boston Red Sox outfielder Jackie Jensen makes a return to the major leagues by signing a $40,000 contract. Jensen had retired in 1960 due to a fear of flying. The layoff will prove detrimental to Jensen, who will hit only .263 with 13 home runs in 1961.
April 27 – The Los Angeles Angels drew a crowd of 11,931 for their home opener against the Minnesota Twins at Los Angeles' Wrigley Field. Ty Cobb, in his last appearance at a ball park, throws out the ceremonial first pitch. Minnesota starter Camilo Pascual spoils the opener by winning, 4–2, sending the Angels to their eighth loss in nine games.
In the second game of the Minnesota Independence Day double-header, Twins slugger Harmon Killebrew hits a three-run home run which will be the only inside-the-park home run of the 573 he will hit in his career.
July 11 – Strong winds at Candlestick Park dominate the first All-Star Game of the season. A capacity crowd sees pitcher Stu Miller blown off the mound in the ninth inning resulting in balk being called, and it enables the American League to forge a 3–3 tie before losing 5–4 in 10 innings.
July 17 – Commissioner Ford Frick decrees that Babe Ruth's record of 60 home runs in a 154-game schedule in 1927 "cannot be broken unless some batter hits 61 or more within his club's first 154 games." Two days later, Frick, an old friend of Ruth, announces that should Ruth's record be beaten after 154 games, the record will carry an asterisk. When asked about the ruling, Roger Maris replies, "A season is a season."
July 31 – At Fenway Park, the second All-Star Game of the year ends in a 1–1 tie as heavy rain halted play. It is the first tie in All-Star history.
August 22 – Roger Maris becomes the first player to hit his 50th home run of the season in the month of August as the Yankees lose to the Los Angeles Angels 4-3. Angels' pitcher Ken McBride tees up the gopher ball in the 6th inning with one on.
August 23 – At Cincinnati's Crosley Field, the Giants hit five home runs in a 12-run ninth inning, beat the Cincinnati Reds 14-0.
October 1 – Before a small crowd at Yankee Stadium, New York Yankees outfielder Roger Maris smacks a 2–0 pitch into right field for his 61st home run of the season (a record that would last until Mark McGwire broke it in 1998). The home run is number 240 for the Yankees, which sets a major league single-season record.
December 2 – MLB clubs vote to curb bonuses. All first-year players not on major rosters, except one minor leaguer, can be drafted by any other club for $8,000. Clubs are expected to be unwilling to pay large bonuses for players who will be subject to a draft for just $8,000.
January 30 – Aaron Ward, 64, second baseman on the Yankees' first championship team in 1923
February 16 – Dazzy Vance, 69, Hall of Fame pitcher who led the NL in strikeouts seven years in a row and won the 1924 MVP award
February 19 – Red Smith, 61, shortstop for the Philadelphia Athletics in the 1920s
March 13 – Joe Berry, 88, catcher for the Philadelphia Phillies for one game in 1902
April 15 – Nick Cullop, 73, pitcher for the Cleveland Naps, New York Yankees and St. Louis Browns, who also won 22 games for the 1915 Kansas City Packers in the outlaw Federal League
April 23 – Jack Barry, 73, shortstop in the Athletics' "$100,000 infield", coach since 1921 at Holy Cross, where he won the 1952 College World Series and posted the highest career winning percentage (.806) in collegiate history
April 28 – Tommy Connolly, 90, Hall of Fame umpire from 1898 to 1931 who worked the first American League game ever, as well as the first contests at Comiskey Park, Shibe Park, Fenway Park, and Yankee Stadium
June 18 – Eddie Gaedel, 36, 3'7" player who made one appearance for the 1951 Browns in a stunt promotion
July 17 – Ty Cobb, 74, Hall of Fame center fielder widely recognized during his lifetime as the greatest player in the sport's history, and holder of more records than any other player including highest lifetime batting average (.367) and most career hits (4,191), runs (2,245), steals (892), games (3,033) and at bats (11,429)
July 17 – Ed Reulbach, 78, pitcher who starred for the Cubs from 1905 to 1913, winning 182 career games
July 18 – Hod Eller, 67, pitcher for the Reds from 1917–1921, including a 1919 World Series game which saw him strike out 6 in a row
August 3 – Thomas Edward Downey, 77, played from 1909 to 1915 for the Reds, Phillies, Cubs, and Bisons.
September 9 – Jesse Barnes, 69, pitcher who won 152 games for the Braves, Giants and Dodgers, including a no-hitter
September 9 – Rube Oldring, 77, outfielder who played mainly for the Athletics, including 4 pennant winners
October 21 – Harry Gleason, 86, infielder/outfielder who played from 1901 through 1905 for the Boston Americans and St. Louis Browns
December 15 – Dummy Hoy, 99, center fielder who scored over 100 runs nine times, and the game's most accomplished deaf player; he threw out the first ball of the 1961 World Series' third game on October 7