Letowski began his career playing junior hockey for the Sarnia Sting of the Ontario Hockey League. Letowski was drafted in the seventh round, 174th overall by the Phoenix Coyotes in the 1996 NHL Entry Draft. The Sting named him Rookie of the Year for the 1994–95 season. Letowski won a gold medal with Team Canada at the World Junior Championships in Switzerland in 1997. A banner depicting his number 17 in Canadiannational team colours hangs at the Progressive Auto Sales Arena in Sarnia, Ontario, where the Sting play. After his third and final season with the Sting, he spent the 1997–98 season with the Springfield Falcons, Phoenix's American Hockey League affiliate. Letowski made his NHL debut in 1998–99 and became a regular in the Coyotes lineup, playing two full seasons. Midway through the 2001–02 season on December 28, 2001, Letowski was traded by the Coyotes, along with Todd Warriner and Tyler Bouck, to the Vancouver Canucks for Drake Berehowsky and Denis Pederson. He was signed by the Columbus Blue Jackets as a free agent on July 3, 2003, and played two seasons there split by a term in Switzerland with HC Fribourg-Gottéron of the Swiss Nationalliga A during the 2004–05 NHL lockout. Letowski joined the Carolina Hurricanes as a free agent on July 6, 2006 and played there for two seasons. During a game against the Pittsburgh Penguins on October 14, 2006, Letowski was hit by the Penguins' Colby Armstrong following a pass in the Penguins' zone. Letowski was knocked unconscious and removed from the ice on a stretcher. There was no penalty on the play. He joined Barys Astana as a free agent on August 3, 2008. Following the conclusion of the 2009–10 season, his second year with Astana, Letowski announced his retirement. Letwoski returned to where he began his career with the Sting, taking up an assistant coaching role on April 17, 2010. He was promoted to head coach on June 14, 2013. On July 9, 2015, Trevor Letowski was hired by the Windsor Spitfires and was designated as their assistant coach, and previous assistant coach, Bob Jones, was hired by the Oshawa Generals.
Letowski began the 2010-11 OHL season as an assistant coach of the Sarnia Sting, however, on February 6, 2011, Dave MacQueen was fired as head coach and GM and Letowski took over serving as interim head coach. In 18 games as the head coach, the Sting went 7-10-1, as they missed the playoffs for the second straight season.
