The appearances led to more prominent roles in films like Passenger 57 (1992), True Romance (1993), Striking Distance (1993), Natural Born Killers (1994), Strange Days (1995), Heat (1995), and The Relic (1997).

[4] His mother, Judith (née Schannault), was a member of the city of Detroit ombudsman staff and his father, Thomas Edward Sizemore Sr., was a lawyer and philosophy professor.

[8] His other early appearances included Lock Up (1989), Harley Davidson and the Marlboro Man (1991), Point Break (1991), Passenger 57 (1992), True Romance (1993), Striking Distance (1993), Natural Born Killers (1994), and Strange Days (1995).

[9][4][10] He had a recurring role on the television series China Beach (1988–1991) as an enlisted man named Vinnie who was in love with Dana Delany's character.

[8][13] He starred in the independent drama film Love Is Like That (1993) with actress and model Pamela Gidley and had a supporting role in Kevin Costner's Wyatt Earp (1994) as Bat Masterson.

[16][18] The next year, television network VH1 aired a six-episode reality TV series called Shooting Sizemore (2007), depicting the actor's life as he struggled to regain his career in the midst of battling long-standing addictions to methamphetamine and heroin.

[22] In the same year, the actor starred in the indie drama film Oranges (2007) with Tom Arnold and Jill Hennessy, which was directed by Syrian director and producer Joseph Merhi.

[18][23][28] Sizemore starred alongside martial arts actor Mark Dacascos in the action film Shadows in Paradise (2010), followed by an appearance as a trucker in an episode of It's Always Sunny in Philadelphia.

[9][29] Sizemore appeared alongside the Insane Clown Posse in the comedy film Big Money Rustlas (2010) and the thriller heist Five Thirteen with Taryn Manning.

[38] In January 2022, he joined the cast of The Legend of Jack and Diane, a feature film described as a female-fronted revenge thriller, directed and written by Bruce Bellocchi.

Originally called "The Bystanders", the group included guitarist and co-writer Rod Castro, Alan Muffterson, Tyrone Tomke, and Michael Taylor.

[55] In 2013, he appeared on the episode "Explosive Relationships" of the talk show Dr. Phil in which he discussed his rise to stardom and the subsequent fallout after his years of struggling with substance abuse.

[63] He denied any wrongdoing and was allowed back on the film set after the Salt Lake County prosecutor's office decided against going forward with the case "due to witness and evidence problems.

"[64] In May 2018, actress Kiersten Pyke, by then 26 years old, filed a lawsuit against Sizemore, claiming that his alleged abuse caused longstanding emotional problems and seeking at least $3 million.

A statement from Sizemore's publicist again denied the abuse, noting that nothing amiss was reported by a Born Killers staff member whose duty was supervising the child actors who were on the set.

Sizemore again denied her claims saying: "Beyond the loss of work and the pain and humiliation this has caused me and my family, the thought that an 11-year old girl would think I violated her, whether it be because she misconstrued some inadvertent touching when the director placed her upon my lap for the photo shoot or someone else instilled this idea in her head for whatever malicious, self-serving reasons, is what devastates me most.

[67] On February 18, 2023, Sizemore suffered a brain aneurysm at his Los Angeles home and was hospitalized at Providence Saint Joseph Medical Center in critical condition.

[68][69][70] On February 27, his representative issued a statement indicating that doctors had determined there was "no further hope" for Sizemore to recover and had "recommended end-of-life decisions" to his family.