He played 15 seasons in Major League Baseball for the Boston Braves (1915–1919), New York Giants (1919–1926), Cincinnati Reds (1926–1927), and the Chicago Cubs (1927–1929).

His paternal grandparents were Wesley Andrew Nehf & Katherina C. Boss who were both born in Germany.

In 1917, Nehf had what is generally thought of as his best season with the Braves, when he went 17-8 with a 2.16 ERA, pitching very consistently, and completing 17 of his 23 starts, with five shutouts, while also finishing seven games on the year.

In 1924, he defeated Walter Johnson in 12 innings in the WS opener, but the Giants lost to the Washington Senators that year.

After many solid, and sometimes great, seasons with the Giants and then being traded to Cincinnati, and then to Chicago, most thought Nehf's career was virtually over.

With the Giants in a tight pennant race against the St. Louis Cardinals, their loss in the 1st game of a doubleheader on September 27, 1928, was made all the more controversial.

Charlie Root was the Cubs' starting pitcher for Game 4 of the 1929 World Series at Shibe Park and was cruising along with an 8-0 lead against the Philadelphia Athletics.

The first batter he faced, Mule Haas, hit a fly ball that Hack Wilson lost in the sun.

Art Nehf Field has served as the site for the 2005 and 2006 NCAA Division III Mideast Regional.