After ten years as Smith's assistant, Williams became head coach at defending national champion Kansas, in 1988, taking them to 14 consecutive NCAA tournaments, four Final Four appearances, two national championship game appearances, collecting an .805 winning percentage, and winning nine conference titles.

In 2003, Williams left Kansas to return to his alma mater North Carolina, replacing Matt Doherty as head coach of the Tar Heels.

In an 18-year period at North Carolina, Williams won three national championships, reached a total of five Final Fours, finished first in the Atlantic Coast Conference regular-season standings nine times, won three ACC tournament championships, one AP National Coach of the Year award, and two ACC Coach of the Year awards.

Williams lettered in basketball and baseball at T. C. Roberson High School in Asheville, North Carolina, all four years.

[7] Williams went on to play on the freshman team at the University of North Carolina at Chapel Hill and study the game under coach Dean Smith.

The 1996–97 team featured future NBA players Paul Pierce, Jacque Vaughn, Raef LaFrentz, and Scot Pollard.

Entering the NCAA Tournament with Pollard (foot stress fracture) and starting shooting guard (later Kansas and UNC assistant coach, and former head coach at Stanford) Jerod Haase (broken wrist) trying to play with injuries, the team was upset in the Sweet Sixteen by the eventual champion, the Arizona Wildcats.

On April 13, Williams announced that he would be leaving Kansas for the North Carolina coaching position, having been courted for it once before in 2000, stating "There's several factors [for my decision] -- my roots, my dream and my family.

Williams quickly reloaded the team with top talent, bringing in recruits like Brandan Wright, Ty Lawson, Wayne Ellington, and Deon Thompson.

After earning a #1 seed in the East Region in the 2007 NCAA Tournament, Williams' team won its first-round game against Eastern Kentucky Colonels 86–65 and its second against Michigan State 81–67.

On March 24, 2007, North Carolina fell to the Georgetown Hoyas in overtime in the East Regional, ending its post-season run.

With Tyler Hansbrough returning to Chapel Hill for his senior season, they were tapped by numerous prognosticators as the favorites to win the NCAA championship.

Two games later, they fell at ACC rival Wake Forest 92–89, but went on a winning streak, including a defeat of archrival Duke by 101–87, Williams' fourth straight victory at Cameron Indoor Stadium.

They also won every game by at least 12 points—all the more remarkable since they upended four teams in the top 15 of the final AP Poll (#10 Gonzaga, #7 Oklahoma, #11 Villanova and #8 Michigan State).

North Carolina finished the regular season at 16–15,[17] dropped to third in all-time wins, and bowed out in the first round of the ACC tournament.

The Tar Heels made it to the NIT championship game versus Dayton, which was played on April 1, 2010, at Madison Square Garden.

"[21] The Tar Heels started out slow during the 2010–11 season, dropping early games to Minnesota, Vanderbilt, and Illinois, and also being blown out by twenty points at Georgia Tech.

It was not until Williams made the difficult decision to start freshman point guard Kendall Marshall over junior Larry Drew II that the Tar Heels returned to their dominant winning ways.

Without Henson, Dexter Strickland and sixth-man Leslie McDonald (who were both sidelined with season-ending injuries) Carolina beat Vermont in the second round of the Tournament.

Carolina turned to first-year point guard Stilman White who helped lead the Heels to an OT win over the Ohio Bobcats in the Sweet 16.

Unlike traditional Carolina teams, the Heels played more guard heavy and relied mostly on their perimeter game to score points.

The Tar Heels grabbed a four seed in the NCAA Tournament with wins against Harvard and Arkansas, but ended their run with a loss to Wisconsin in the Sweet Sixteen.

In the 2016 NCAA tournament, North Carolina beat Florida Gulf Coast, Providence, Indiana, and Notre Dame, and Syracuse in the Final Four, to earn a spot against Villanova in the national championship game.

In the 2017 NCAA Tournament, North Carolina defeated Texas Southern 103–64, Arkansas 72–65, Butler 92–80, Kentucky 75–73, Oregon 77–76 and Gonzaga 71–65 to win its third national title in the Roy Williams' era.

After a dismal 21 point loss to the Louisville Cardinals, the Tar Heels would lose only one more game, finishing the regular season 26–5 overall, 16–2 in the ACC, tied atop the conference with the Virginia Cavaliers.

Adding great and consistent offensive production during the season, Coby White averaged 16.1 PPG in his freshman year as a Tar Heel.

On February 27, 2021, Williams won his 900th game, becoming the fastest men’s coach to reach the milestone in D-1 history, after an upset win over #11 Florida St., 78–70, in Chapel Hill.

In 2009, Algonquin Books published Williams' autobiography, Hard Work: A Life On and Off the Court, co-written by Tim Crothers.

[27] In March 2021, Williams and his wife Wanda donated $3 million to the University of North Carolina, to support various scholarships for UNC.

[28] Williams also donated $600,000 in the wake of the COVID-19 pandemic to provide scholarships for an extra year of eligibility for UNC spring sport athletes who had their 2020 seasons cut short.