As a senior in 2005, he was named All-State First-team and All-Metro League Mountain Division Offensive MVP and Defensive Co-MVP.

Mays played for the West Team in the 2006 U.S. Army All-American Bowl game alongside future USC teammates Mitch Mustain and Stafon Johnson.

While considering offers from USC, Washington and Miami, Mays elected to commit to the University of Southern California after being recruited by defensive back coaches Rocky Seto and Greg Burns.

Mays received an athletic scholarship to attend the University of Southern California, where he played for head coach Pete Carroll's USC Trojans football team from 2006 to 2009.

Mays got the start at free safety his freshman year after Josh Pinkard went down with a season-ending injury in their first game against Arkansas.

According to Carroll, Mays was clocked at an astonishing 4.25 in the 40-yard (37 m) dash, .01 seconds slower than the record set at the 2008 NFL Combine by Tennessee Titans running back Chris Johnson.

[13] His most impressive game of the season came during week 10 against California, where he posted 10 tackles and deflected 3 passes which helped hold one of the best offenses in the nation 14 points below its average in the 24–17 win.

After the 2007 season, Mays was listed by ESPN The Magazine in an article titled "Workout Warriors", honoring college football's most physically talented players.

Mays stated in a Los Angeles Times interview on November 10 that he would decide whether or not to forfeit his senior year at USC to enter the 2009 NFL draft after the 2008 post season, saying that a big factor in his decision would come from his father and head coach Pete Carroll.

Mays had a spectacular performance in the game, delivering several big hits which jarred balls loose from the receivers' hands.

The Trojans would go on to face Penn State in the 2009 Rose Bowl, where the defense shut down one of the most explosive offenses in the country in the 38–24 win.

Mays ended his junior season as a finalist for the Jim Thorpe Award after being beaten out by Ohio State cornerback Malcolm Jenkins.

On January 13, two days before the deadline for college players to declare for the Draft, Mays announced that he would return to USC for his last year.

Mays was regarded as unanimous first-round pick in the 2009 NFL Draft but opted to return to continue to develop and to complete his education at Southern California, citing the importance of graduating to himself and his parents as well as giving his last shot at leading USC to the BCS National Championship.

[18][19] In a Lindy's Football article, Mays stated that he wanted to play a different role in the defensive secondary that would call him to be more involved in the action.

The usual duties of a free safety in Pete Carroll's defense calls for him to be a center fielder preventing plays being made deep downfield, keeping him from doing much else in the box.

Prior to his first season, Mays was considered one of the top talents for the 2010 NFL draft and frequently drew comparisons to Adrian Wilson for his size and Sean Taylor for his hitting ability, .

[25][26][27][28][29][30] Mays participated in the 2010 Senior Bowl, but played sparingly, making his interception of Cincinnati quarterback Tony Pike in the second quarter being his only highlight.

[31] According to Sports Illustrated's Tony Pauline, Mays "looked stiff and mechanical with his defensive back fundamentals and really showed limited skills in pass coverage drills", and was therefore projected to outside linebacker by some teams.

On March 31, 2010, Mays participated at USC's pro day, but only ran positional drills for team representatives and scouts in attendance.

At the conclusion of the pre-draft process, Mays was projected to be a second round pick by the majority of NFL draft experts and scouts.

He fell from his top ten and first round grade the previous year, due to concerns over his coverage ability and lack of perceived drive to work on his weaknesses.

[41][42] In a post-draft interview, San Francisco 49ers executive Trent Baalke insisted that, despite the addition of Mays, then-current veteran strong safety Michael Lewis would be the starter for the 2010 season.

[56] On September 14, 2015, Mays re-signed with the Raiders due to starting safeties, Nate Allen and Charles Woodson both sustaining injuries in the first regular season game.

[58] On July 23, Mays was released by the Bengals after learning that he would be dealt an additional suspension for violating the NFL's substance abuse policy again.

[59][60] On October 9, 2017, Mays was added to the Saskatchewan Roughriders of the West Division of the Canadian Football League (CFL), and he played one game for them the following month.

Mays' work with the USC secondary players was credited for their much improved tackling in the 2023 Holiday Bowl in San Diego.