The Twins played their first ever regular season game at Yankee Stadium. Harmon Killebrew collected the first hit in Twins history, leading off the 4th with a single to center. Twins pitcher Pedro Ramos and Whitey Ford were locked in a scoreless duel until Bob Allison led off the 7th with a home run, the first in Twins history. The Twins went on to win their first game 6-0 as Ramos pitched a complete game, 3-hit shutout versus the eventual 1961 World Series champs. Ramos held Yogi Berra, Mickey Mantle and Roger Maris to a combined 1-for-11, with Berra singling in the 1st. Ramos did not allow a baserunner after the 5th inning. Roger Maris would establish a new single season home run record with 61 that year.

The Twins would go on to a 5-1 record before playing their first home game in front of a crowd already deep in the throes of pennant fever. They would lose their first game in Bloomington, however, 3-5 to the new Senators, and finish their inaugural season 70-90, 7th place in the America League.