Born in Madison, Wisconsin, Nichols entered the major leagues in 1890 with the Boston Beaneaters and was an instant success. Nichols went 27-19 with a 2.23 ERA and 222 strikeouts and began 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) and a career high of 35 in 1892.
Nichols suffered his first losing season in 1900 when he went 13-16 but 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, 1868 strikeouts and a 2.95 ERA. He was a part of five National League championship teams, all with the Boston Beaneaters (1891 - 1893, 1897, 1898). His 361 victories ranks 7th all-time, and his 5056 1/3 innings pitched ranks 11th all-time.
After baseball, Nichols dabbled in the motion picture industry and opened bowling alleys in the Kansas City area. An accomplished bowler himself, Nichols would eventually win the Class A bowling championship at age 64.