Cammalleri played the majority of his significant minor hockey with the Toronto Red Wings. After a brief stint in Ontario Provincial Junior ‘A’ with the Bramalea Blues, he moved on to play college hockey for the Michigan Wolverines for three seasons.
Cammalleri was drafted by the Los Angeles Kings in the second round (49th overall) of the 2001 NHL Entry Draft and began his career with the Kings, making his NHL debut on November 8, 2002 against the Ottawa Senators and picking up his first NHL point with an assist. He scored his first NHL goal in his fifth game on November 16, 2002 against the Edmonton Oilers, the game-winner, in a 4–1 victory. Subsequently, he would spend some time with the AHL‘s Manchester Monarchs. In the 2004–05 AHL season, Cammalleri was awarded the Willie Marshall Award for leading the league in goals, scoring 46.
He was a member of the 2007 Canadian IIHF World Championships team that won gold in a 4–2 win against Finland in Moscow. Cammalleri received a new 2 year contract worth $3.1 million in 2007–08 and $3.6 million in 2008–09 for an average cap hit of $3.35 million per year. At the start of the 2007–08 season he was named an alternate captain for the Kings. On September 29, 2007, he scored the first ever regular season NHL goal in Europe in a 4–1 win against the Anaheim Ducks as the league opened the regular season with games at The O2 in London.
On June 20, 2008, Cammalleri was traded to the Calgary Flames in a draft day three-way deal between the Anaheim Ducks and the Kings. The Flames acquired Cammalleri from the Kings in exchange for the 17th overall pick in the draft. Los Angeles then dealt the 17th selection and its 28th pick to the Ducks for their 12th overall pick. Cammalleri scored his first career NHL hat trick on November 27, 2008 in Calgary’s 4–3 win in a game with the Vancouver Canucks. Cammalleri finished the season with a career high 82 points, 39 goals and 43 assists.
On July 1, 2009, Cammalleri signed a five-year contract worth US$30 million with the Montreal Canadiens. On October 24, 2009, he got a hat trick and scored the overtime winner to help the Canadiens beat the New York Rangers 5–4. On December 4, 2009, the night of the Canadiens’ 100th anniversary, he scored his second hat trick of the season in a 5–1 win for the Canadiens against the Boston Bruins. On December 28, 2009, Cammalleri also scored the Montreal Canadiens’ 20,000th franchise goal against the Ottawa Senators. Cammalleri was the team leader in goals with 26 when he suffered a knee injury on January 30 after a collision with Ottawa Senators defenseman Anton Volchenkov missing 17 games until mid-March. Cammalleri returned on March 24, 2010, in a game versus the Buffalo Sabres. He would go goal-less for the final 9 games of the regular season, while only registering two assists. However, in the playoffs Cammalleri found his goal scoring touch. By the end of the Conference Finals (in which Montreal was eliminated) Cammalleri lead the league in goal scoring with 13. No other player scored as many goals as him in the playoffs, even those on teams that reached the final. His 13 goals were highlighted with scoring 7 goals in a seven-game series against the Pittsburgh Penguins. The feat tied a Canadiens team record held by Maurice Richard (2), Jean Beliveau, Bernie Geoffrion, Guy Lafleur, Frank Mahovlich and Marcel Bonin. Cammalleri was given a one-game suspension for the 2010–11 season opener after a slash to New York Islanders rookie Nino Niederreiter in a preseason game.