Upshall was selected by the Nashville Predators with the No. 6 pick in the 2002 NHL Draft, making it an even more eventful year. He already had been named the top rookie in the Western Hockey League and Canadian Hockey League for 2011-12, skated in the CHL Top Prospects Game and won a silver medal with Canada at the 2012 World Junior Championship.

Upshall would continue his winning ways as a professional. In 2003-04 he won the Calder Cup with Milwaukee of the American Hockey League, and in 2005-06 he helped Milwaukee reach the Calder Cup Finals.

He made his NHL debut Oct. 15, 2002, against the New York Islanders, and scored his first NHL goal four days later against the New York Rangers. After eight games, the Predators returned Upshall to Kamloops of the WHL. He won a second straight silver medal with Canada at the 2003 World Junior Championship.

Upshall would play 15 NHL games over his first two seasons with the Predators before getting eight goals and 24 points in 48 games in 2005-06. Nashville traded Upshall to the Philadelphia Flyers on Feb. 15, 2007 with Ryan Parent and first- and third-round draft picks in 2007 for Peter Forsberg. Upshall had 14 goals and 30 points in 2007-08 to help the Flyers reach the Eastern Conference Final.

On March 4, 2009, the Flyers traded Upshall to the Phoenix Coyotes with a 2011 second-round draft pick for Daniel Carcillo. Upshall scored 18 goals for the Coyotes in 2009-10, and got his first NHL hat trick Jan. 21, 2010, against goaltender Dan Ellis and Nashville. The Coyotes traded Upshall to the Columbus Blue Jackets with Sami Lepisto for Rostislav Klesla and Dane Byers on Feb. 28, 2011.

He signed as a free agent with the Florida Panthers on July 1, 2011, and in 2011-12 helped Florida make the Stanley Cup Playoffs, where he had one goal and three points in seven games. He was fourth in goals (15) and tied for second in points (37) on the Panthers in 2013-14.

After four seasons with Florida, Upshall signed as a free agent with the St. Louis Blues on Oct. 5, 2015. He had 14 points (six goals) in 70 games in his first season with the Blues, who reached the Eastern Conference Final.