He played college football for the Notre Dame Fighting Irish, earning unanimous All-American honors and receiving multiple national awards.

Te'o began his varsity career in 2006 with stellar play that won him selection to the second-team all-state roster as a sophomore.

He received first-team all-state honors while totaling 90 tackles and five sacks on defense and 400 rushing yards and ten touchdowns as a running back.

During his senior year, Te'o helped lead Punahou to its first-ever state championship in football during the 2008 season.

He amassed 129 tackles, including 11 sacks, forced three fumbles, tipped four passes and totaled 19 quarterback hurries.

Major recruiting service Rivals.com listed him as a five-star recruit—the first from Hawaii since Jonathan Mapu in 2002—and ranked him second among inside linebackers only behind Vontaze Burfict.

Te'o entered his first college game at the start of the second defensive series early in the second quarter versus Nevada on September 5, 2009.

Te'o was a finalist for the Butkus Award and the Lott Trophy and was selected as the 2011 FBS Independent Defensive Player of the Year.

[21] Te'o was named a second-team All-American by the Associated Press, Walter Camp Football Foundation, Rivals.com, Phil Steele and CNNSI.

[21] During the season, Te’o was the leading tackler and leader in interceptions for a 12–0 Notre Dame team which had the second-ranked scoring defense (10.33 points per game) in the country.

[24] One of three finalists for the Heisman Trophy, Te'o eventually finished second in the voting to Texas A&M quarterback Johnny Manziel.

[39] His comparably slow time of 4.82 in the 40-yard dash was disappointing, but he promised to "do a lot better" at his Notre Dame pro day.

[41] At Notre Dame Pro Day on March 26, Te'o ran faster according to ESPN's Todd McShay (hand-timed 4.75 and 4.71).

[42] He was selected in the second round, 38th overall by the San Diego Chargers,[43] as the second inside linebacker in the draft behind Alec Ogletree.

[61] He was elevated to the active roster on January 9, 2021, for the team's wild card playoff loss against the New Orleans Saints, and reverted to the practice squad after the game.

[64] He is the son of Brian and Ottilia Te'o and has five siblings: sisters BrieAnne, Tiare, Eden, Maya and brother Manasseh.

[65] In high school, Te'o had a 3.52 grade-point average and did volunteer work with the Shriners Hospital, Head Start preschool program, Hawai'i Food Bank and Special Olympics.

[67][68] In February 2020, Te'o became engaged to his girlfriend, personal trainer and beauty consultant Jovi Nicole Engbino.

[70] Te'o is a close friend of quarterback Tua Tagovailoa, a fellow Samoan NFL player who grew up in Hawaii, and refers to Tagavailoa as his "little brother".

[72] Te'o said that his girlfriend, Stanford University student Lennay Kekua, had been injured in a car accident, and was discovered during her treatment to have leukemia.

[74] Many sports media outlets reported on these tragedies during Te'o's strong 2012 season and emergence as a Heisman Trophy candidate.

[75] After receiving an anonymous email tip in January 2013, reporters Timothy Burke and Jack Dickey of the sports blog Deadspin conducted an investigation into Kekua's identity.

On January 16, they published an article alleging Kekua did not exist and pointed to a man named Ronaiah "Naya" Tuiasosopo (/roʊˈnaɪə ˌtuːjɑːsoʊˈsoʊpoʊ/ roh-NY-ə TOO-yah-soh-SOH-poh) as involved in the hoax of a relationship with Te'o.

[78] On the same day the Deadspin article was published, Notre Dame issued a statement that "Manti had been the victim of what appears to be a hoax in which someone using the fictitious name Lennay Kekua apparently ingratiated herself with Manti and then conspired with others to lead him to believe she had tragically died of leukemia.

[85][86][87][88] In response to the growing suspicions that he was involved in the hoax, Te'o agreed to a January 18, 2013, interview with sports journalist Jeremy Schaap in which he maintained his innocence.

[89] Te'o said he was angered and confused by the December 6 phone call and had continued to speak of Kekua because the situation was unclear to him.

[89] Te'o further explained that Tuiasosopo claimed to be a cousin of Lennay Kekua, and that the two of them had communicated online over the last several years and met once in person at the 2012 Notre Dame/USC game.

"[90][91][92] In an appearance on Dr. Phil on January 31 and February 1, Tuiasosopo confessed to the hoax and admitted to falling in love with Te'o and using the Kekua identity.

[95] Te'o's experience was the subject of a Netflix documentary, Untold: The Girlfriend Who Didn't Exist, which was released in August 2022.