He is perhaps best known as Edd (Double D) from Ed, Edd n Eddy. His notable anime roles include Athrun Zala from Gundam Seed, Peach Man (Tokajin) from InuYasha, Ghost Cat and Curry Man from Ranma 1/2, and Julian Star from Cardcaptors. Other roles include Forge from X-Men Evolution and Baby Bugs, Baby Daffy and Baby Tweety from Baby Looney Tunes, Sideswipe from Transformers Armada and Aerrow from Storm Hawks. He is also known for voicing Krypto from Krypto the Superdog, Sonic the Hedgehog's singing voice in Sonic Underground, Marky (the tallest roach) in Oggy et les Cafards, and the title character and the alien Billy of Martin Mystery.
Samuel started voice-acting in 1990. He was also born in the same place as Matt Hill. The two are often cast together as friends, most famously as Edd (Vincent) and Ed (Hill) from Ed, Edd, and Eddy, as the two protagonists of the Gundam SEED franchise; Athrun Zala (Vincent) and Kira Yamato (Hill), and as Chris (Vincent) and Danny (Hill) from Monster Buster Club and as Aerrow (Vincent) and Finn (Hill) on Storm Hawks. He is sometimes credited as Sam Vincent and Sam Khouth. His brother Gabe Khouth is also a voice actor, and he has worked alongside Samuel on Gundam SEED and Gundam 00.