Nichols played minor league baseball for three different teams until September 1889, when he signed for the Boston Beaneaters. After making his debut the following season and spending twelve seasons with the Beaneaters, Nichols spent a two-year sojourn in the minor leagues. He was dealt to the St. Louis Cardinals in 1904 and subsequently played for the Philadelphia Phillies, with whom he played his final game on May 18, 1906. He is most famous for being the youngest pitcher to join the 300 win club.
Nichols was born on September 14, 1869 in Madison, Wisconsin. He was the seventh child born to a butcher and a housewife. The family moved from Madison to Kansas City, Missouri when Nichols was a child. While his siblings worked in the family butcher shop, Nichols pursued baseball.
Nichols entered the major leagues in 1890 with the Boston Beaneaters. Nichols recorded a 27–19 win-loss record, a 2.23 ERA and 222 strikeouts, beginning a string of ten 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.
Nichols had his first losing season in 1900, when he went 13–16. He improved to 19–16 the following year. After the 1901 season, Nichols purchased an interest in a minor league franchise in Kansas City. He left the Beaneaters to manage and pitch for the Kansas City club, where he won a total of 48 games in 1902 and 1903. After a two-year hiatus from the major leagues, Nichols returned to the 20 win plateau for the eleventh and final time in his career in 1904 for a new team, the St. Louis Cardinals. He finished his career in 1906 with the Philadelphia Phillies, who picked him up off waivers in 1905. Nichols retired with 361 wins, 208 losses, 1,868 strikeouts and a 2.95 ERA. Nichols's win total was exceeded at the time only by Cy Young. Nichols was a part of five National League pennant winners, all with the Boston Beaneaters (1891–93, 1897, 1898).
After baseball, Nichols dabbled in the motion picture industry, partnering with Joe Tinker in a business that distributed movies to theatres in the midwest. An accomplished bowler, Nichols also opened bowling alleys in the Kansas City area. He won Kansas City's Class A bowling championship at age 64.
In October 1952, the 83-year-old Nichols was admitted to Menorah Hospital in Kansas City to investigate a complaint with his neck. Doctors ordered tests, but Nichols would not submit to them until after the seventh game of the World Series ended. He was later diagnosed with carcinomatosis, cancer that had spread throughout his body. He died on April 11, 1953.