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Cena began professional wrestling in 1999 and signed with the World Wrestling Federation in 2001, where he began in its then-developmental territory Ohio Valley Wrestling. After debuting on the main roster on WWE SmackDown! in 2002, he rose to prominence as a brash heel rapper, before becoming the company's franchise player from the mid-2000s to the mid-2010s. He wrestled on a part-time schedule from 2017 until his retirement in 2025. His run as a face from 2003 to 2025 was the longest continuous portrayal of a heroic character in WWE history.

Cena held numerous championships and accomplishments in WWE, including the WWE Championship a record 14 times, the World Heavyweight Championship three times, the WWE United States Championship five times, the WWE Intercontinental Championship once, the World Tag Team Championship twice, and the WWE Tag Team Championship twice. He is the 35th Triple Crown and 25th Grand Slam champion, won the Royal Rumble match twice, the Elimination Chamber match four times, the Money in the Bank match once, and headlined multiple major WWE pay-per-view and livestreaming events. Cena's full-time career received mixed critical and audience reception, with praise for his character work and promotional skills but criticism for his perceived over-representation and on-screen dominance relative to other wrestlers. In contrast, his later career was more positively received.

Cena began acting in 2006 and has done both comedy and action films, receiving praise for his roles in Trainwreck, Blockers, and The Suicide Squad. He has also starred in films such as The Marine, Bumblebee, and F9, as well as portraying the title character on the TV series Peacemaker. In music, he released the rap album You Can't See Me in 2005, which peaked at No. 15 on the Billboard 200. Cena is also known for his charity work, granting more than 650 wishes for the Make-A-Wish Foundation, the most in the organization's history.