Knothe was born in Bayonne, New Jersey and graduated from high school in 1917. He began his professional baseball career in 1922 at the age of 24 with the Newark Bears of the International League. He graduated from the University of Pennsylvania in 1925. In 1926, he posted a .354 batting average with the Lawrence Merry Macks of the New England League.
In 1928, he had a career year with the Pueblo Steel Workers of the Western League when, he hit .318 in 164 games with 41 doubles, 17 triples, and six home runs. His impressive performance earned him a job with the Kansas City Blues of the American Association. His strong defensive play helped the Blues win the 1929 Little World Series over the Rochester Red Wings. In 1931, the Blues sent Knothe to the New Orleans Pelicans of the Southern Association where, he became known as one of the best defensive shortstops in the league.
The Philadelphia Phillies selected Knothe in the Rule 5 draft on September 30, 1931. He made his major league debut with the Phillies at the relatively late age of 34 on April 25, 1932 in a game against the Boston Red Sox that, also featured his brother Fritz playing as the Red Sox third baseman. Four days later at Philadelphia's Baker Bowl, he collected his only major-league hit, a double off of Brooklyn pitcher Van Lingle Mungo. The presence of veteran player Dick Bartell relegated Knothe to the role of utility player. After only one month in the major leagues, a new Depression-era rule limiting teams to 23 players would lead the Phillies to send him to the Fort Worth Cats of the Class A Texas League.

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