After graduating from Venice High School, Guthrie attended LSU where he led the team in ERA in 1985 and was all SEC first team in 1986. He was later selected by the Twins in the 7th round of the 1987 amateur entry draft and played in Minnesota from 1989 to 1995. On November 6, 1996 he signed as a free agent with the Los Angeles Dodgers, where he played until the close of 1998. Following his membership with the Dodgers, Guthrie was a player for the Boston Red Sox, Chicago Cubs, Oakland Athletics, Toronto Blue Jays and the New York Mets. Throughout his entire professional career (1989–2003) Guthrie earned over 15 million dollars.