Nichols signed with the Boston Beaneaters in September 1889 and entered the major leagues in with them in 1890. Nichols recorded a 27–19 win–loss record, a 2.23 earned run average (ERA) and 222 strikeouts, beginning a string of 10 consecutive seasons with 20 wins or more. Nichols also had a major league record seven 30-win seasons in this time (1891–1894, 1896–1898) with a career high of 35 in 1892. The Beaneaters won several pennant races during Nichols' tenure, finishing in first place five times between 1891 and 1898. The team had 102 wins per season in 1892 and 1898, which stood as franchise highs until 1998. Baseball-Reference.com calculates that Nichols led the team in wins above replacement in 1890 and 1892 through 1898.