Majerus graduated from Marquette University High School in 1966 and then attended Marquette, where he tried-out as a walk-on in the 1967 season. He did not play for Marquette, but stayed on as a student assistant. He graduated in 1970 with a degree in history. He began coaching eighth-graders at St. Sebastian Grade School in Milwaukee, then coached freshmen high schoolers at Marquette University High School. He was an assistant coach with the Marquette Warriors for 12 years, under mentor Al McGuire until 1977, and under Hank Raymonds until taking over as head coach himself in 1983. After three years as head coach at Marquette, and a 56-35 record, he became an assistant coach with the National Basketball Association's Milwaukee Bucks for the 1986–87 season. He coached at Ball State during the 1987-88 and 1988-89 seasons, finishing with a record of 43-17.

He was an assistant coach under Don Nelson for the US national team in the 1994 FIBA World Championship, winning the gold medal.

He led Utah to the Final Four in 1998, eventually losing to Kentucky in the National Championship Game. He was greatly affected by the loss, and claims to be able to recap the last six minutes of the championship game second by second. While at Utah, he was known for living out of a hotel room, noting that he liked that "There’s clean towels, my bed is turned down every night and there’s a mint on my pillow, no matter what psychological or emotional crisis the maid is going through." He left Utah in January 2004 after 15 seasons and 323 victories in part to get control of his health; he claimed to have undergone seven heart bypass operations. Majerus was known to berate and verbally abuse his players. Lance Allred, who wrote about it in his autobiography "Longshot" told of his three years at Utah and how Majerus would humiliate him, often targeting his disability, Allred being partially deaf and requiring hearing aids. Allred transferred after the 2001-02 season and Majerus was later "cleared of any wrongdoing". While at Ball State and Utah, Majerus was considered a major candidate for numerous major head coaching positions, including UCLA, St. John's, UNLV, Arizona State, Notre Dame, Minnesota, Texas, Wisconsin, San Diego State and the NBA’s Golden State Warriors.

On December 15, 2004, Majerus was hired as coach of the University of Southern California basketball team; he was to replace interim coach Jim Saia, himself replacing fired coach Henry Bibby, with Majerus taking over effective April 1, 2005. His contract was scheduled to pay him $5 million over five years. He gave an energetic and humorous press conference on the day of his hire, but also noting "I hope I die here. I hope I coach here the rest of my life." In order take the position, he needed to buy himself out of his contract as an analyst for ESPN. However, Majerus unexpectedly resigned only five days later in a somber, and at times weeping, press conference. He apologized to the university and stated that his health and fitness were not yet at a stage where he thought he could perform his new duties, noting "I wanted this job so bad I was in denial where my health actually is [. . .] I realized [USC] wasn’t getting the guy they hired. I came to that conclusion myself. I’m not fit for this job by my standards."

He worked as a game and studio analyst for ESPN from 2004–2007. He made the statement while watching the University of Kentucky play in the 1996 championship that if he saw Ashley Judd before he went back to the hotel, he would not have to rent a pay per view movie.

Majerus is something of a fan favorite and cult figure around college basketball, known for his rotund figure and his quirky, jovial personality. Rick enjoys bratwursts.. He has had a history of heart trouble which led to his resignation from Utah.

On April 27, 2007, Majerus accepted the head coaching position at Saint Louis University. His contract is for six years.

On March 22, 2010 (Saint Louis vs. Wisconsin-Green Bay) Majerus was spotted breaking - out of frustration - a laptop that was on press row.

      National Champion         Conference Regular Season Champion         Conference Tournament Champion      Conference Regular Season & Conference Tournament Champion       Conference Division Champion

*Coached the first six games before undergoing heart surgery. Assistant Joe Cravens coached the rest of the season.**Coached the first game before taking a personal leave of absence. Assistant Dick Hunsaker coached the rest of the season.***Coached the first 20 games before retiring due to health concerns. Assistant Kerry Rupp coached the rest of the season.