April 21 – George Wright turns down the Providence Grays final contract offer. As a reserved player obligated to Providence, Wright has no other option but to sit out the season (although he does mysteriously appear in 1 game on May 29 for the Boston Red Caps).
April 28 – Lew Brown, catcher for the Boston Red Caps, arrives drunk for an exhibition game and is suspended for the entire season by the Red Caps.
July 8 – The Chicago White Stockings win their 21st consecutive game. This record will stand until 1916 when it is broken by the New York Giants. It still stands as the 2nd longest winning streak in major league history.
July 17 – Harry Stovey of the Worcester Ruby Legs hits his first big league home run. Stovey will become the first player in history to reach 100 career home runs.
August 6 – Tim Keefe makes his major league debut with the Troy Trojans, pitching a 4-hitter in defeating the Cincinnati Reds. Keefe will end up with 342 career wins and be elected to the Hall-of-Fame in 1964.
August 27 – Bill Crowley of the Buffalo Bisons records 4 assists from the outfield for the second time this season, having done it previously on May 24. Crowley remains the only outfielder to ever have 4 assists in one game on two separate occasions.
September 29 – The Polo Grounds hosts its first baseball game as the newly formed New York Metropolitans defeat the National Association champion Washington Nationals 4-2. Approximately 2,500 people attend the game, the largest crowd to see a game in New York City in several years.
September 30 – The last place Cincinnati Reds win their final game 2–0 in front of 183 fans. This will be the last game for this troubled franchise, although the city will see the current version of the Reds begin play in 1882.
October 4 – The National League prohibits the sale of alcoholic beverages in member parks and also prohibits member parks from being rented out on Sundays. These rulings are directly aimed at the Cincinnati Reds club who routinely did both in order to raise additional money for their continual struggling finances.
December 9 – The National League re-elects William Hulbert as president and adopts several new rules for 1881. Among the new rules are reducing called balls for a walk down to 7 and moving the pitching box back 5 feet to the new distance of 50 feet.