Guthridge initially gained recognition after serving for thirty years as Dean Smith's assistant at the University of North Carolina and summing many wins as a result.

While a student at Kansas State, Guthridge played guard under head coach Fred "Tex" Winter, and helped the team advance to the 1958 Final Four.

In five years on Winter's staff, Guthridge helped lead the Wildcats to a 93–43 (.684) record, a pair of Big Eight Conference crowns, and the NCAA Final Four in 1964.

In 1976, he also served as an assistant coach to Smith as the United States won the gold medal in men's basketball at the Summer Olympics in Montreal.

[3] Dean Smith unexpectedly retired as head basketball coach at North Carolina just two months before the start of the 1997–98 season, and Guthridge was immediately named his successor.

With a wealth of returning talent, Guthridge instituted a "six starters" system, whereby the team's top six players, Antawn Jamison, Vince Carter, Ed Cota, Shammond Williams, Ademola Okulaja, and Makhtar N'Diaye rotated positions in the starting five.

The next season, North Carolina earned a #3 seed in the West regional of the NCAA tournament, but was upset in the first round by Weber State in a late game in Seattle.

Seeded eighth in the South region, North Carolina upset top-seeded Stanford in the second round and continued to the Final Four, where they lost to Florida.