May 2 – The International Association commences regular season play with 12 teams as follows – Auburn, Binghamton Crickets, Brooklyn Blues, Buffalo Bisons, London Tecumsehs, Manchester Reds, New Bedford Whalers, New Haven Elm Citys, Pittsburgh Alleghenies, Rochester Flour Citys, Syracuse Stars and the Worcester Reds. The New York Clipper declares the new IA to be a "major league."
May 7 – The IA's Auburn and Brooklyn teams disband leaving the circuit with 10 teams.
September 14 – The Indianapolis Blues and Boston Red Caps play an experimental exhibition game in which every pitch thrown is called a ball or strike and only allowing 6 balls before a walk is issued.
September 30 – The National League completes its schedule, marking the first time in professional baseball that a full schedule has been played by all member teams.
October 2 – The Buffalo Bisons of the International League defeat the National League champion Boston Red Caps behind the pitching of Pud Galvin. The victory over the Red Caps gives Galvin a win over each team in the NL. He finishes the 1878 season with a combined 10–5 record against the NL clubs. Buffalo will become a member of the National League in 1879.
October 8 – The Buffalo Bisons defeat Utica and lay claim to the International Association pennant as well. The league will ultimately award the pennant to Buffalo in early 1879
October 18 – The Indianapolis Blues come up short $2,500 and are unable to account for the money. The players receive $60 each as payment for the remainder of the season. This event signals the end of the Blues.
December 4 – The National League changes the rules so that now every pitched ball is called a ball or a strike. 9 balls will now result in a walk to the batter. The rules are also changed regarding the batting order. The first batter in a new inning shall now be the next batter in the order after the last batter that ended the previous inning.
December 5 – The National League abolishes all bound outs, including foul balls on 3rd strikes.
December 29 – The Professional Baseball League of Cuba is founded in Havana with Habana defeating Almendares 21-20. The league is known today as the Cuban League and ran continuously until March, 1961, when the Cuban government, ran by Fidel Castro, abolished professional baseball.