The Americans played its first game on April 26, 1901, losing to the Baltimore Orioles by a score of 10-6. Win Kellum was the team’s first starting pitcher, but made only five other appearances that season. Denton True “Cy” Young, already an 11-season National League veteran, started, and lost, the team’s second game. 

The Americans played its first home game at the Huntington Avenue Baseball Grounds on May 8, 1901. The Americans’ starting pitcher was the 34 year old Young, and the Americans prevailed by a score of 12-4, pounding out 19 hits. 1901 was the first of Young’s eight seasons with the Americans.
The 1901 team was managed by future Hall of Famer Jimmy Collins, making his managerial debut, and finished the season in second place with a record of 79 wins, 57 losses, and 2 ties, four games behind the Chicago White Sox. The team was dominant at its home park, recording 49 wins against 20 losses, outscoring its opponents 383-252.

First baseman Buck Freeman finished the season with a .339 batting average, hit 12 home runs, and batted in 114 runs, finishing second to Napoleon Lajoie in the latter two categories. Manager and third baseman Collins managed a .332 batting average and batted in 94 runs. Shortstop Fred Parent and center fielder Chick Stahl both finished with batting averages above .300. The regular seven players (all but the pitcher and catcher position) each stole 11 or more bases. First baseman Buck Freeman committed 38 errors; second baseman Hobe Ferris committed 61 errors; shortstop Fred Parent committed 63. Jimmy Collins made 50 errors at third base. The catcher position combined for 44 errors. The tallest member of the regular starting lineup was five feet, ten inches.

Cy Young led the American League in wins (33), strikeouts (158), earned run average (1.62), and fielding percentage. Young pitched 38 complete games and five shutouts. Ted Lewis and George Winter each recorded 16 wins. (Lewis earned the team’s fist save.) Of the 138 games the team played, pitchers recorded 123 complete games.

With the exception of the catcher position, the team fielded a regular seven players: only 64 at bats were recorded by other than the regular seven. Five players led the American League in games played at their position. Two, including hitting star Freeman, led the league in errors, and Freeman was ejected from five games.

In the inaugural American League season, the Boston Americans attendance total exceeded all but one American League team and all but two National League teams.