He was originally drafted by the Vancouver Canucks and played three seasons in Vancouver. The Canucks traded Neely and a draft pick (1st choice, 3rd overall in the 1987 NHL Entry Draft, used to get Glen Wesley) to the Boston Bruins for Barry Pederson. Almost immediately, it became apparent that the Bruins had received the better of the deal. In his first full season following the trade, Neely's 36 goals led the club, and his 72 points more than doubled his previous year's performance.

Neely's success stemmed largely from his hard, accurate shot, quick release, and his willingness to engage in the more physical aspects of the game. At 6 ft 1 in and 215 lb, Neely was as devastating with his body checks and fists, as he was with his goal scoring exploits. He became the archetype of the ultimate power forward (in draft after draft, general managers would say that they needed to find a "Cam Neely" type).

Cam Neely would play ten seasons with the Bruins, and though increasingly injury-prone, recorded some remarkable scoring feats. Only Wayne Gretzky, Mario Lemieux, and Brett Hull scored a better goals per game average over the course of an NHL season than Neely did with his 50-goals-in-49-games in the 1993-94 season. Also, only ten players in NHL history scored a better goals per game average over their career than Neely. He reached the fifty goal mark three times, played in five All-Star games, and was named the league's Second Team All-Star at right wing in 1988, 1990, 1991, and 1994.

Scoring 50 goals in 50 games is considered the bench-mark of great goal scorers. Maurice Richard, Mike Bossy, Wayne Gretzky, Brett Hull, Mario Lemieux, Alexander Mogilny, and Jari Kurri are the only other players to score 50 goals in 50 games or less. In the 1993-94 season Neely scored his 50th goal in his 44th games, only Gretzky has scored 50 goals in fewer games. Unfortunately, Cam Neely's 50 in 44 does not count in the record books because the record books state "50 goals in 50 team games or less". Neely was injured for much of the 1993-94 NHL season and did not score his 50th goal in his team's 50th game or less.

In addition, Neely's intense efforts to come back time and again from his devastating injuries were recognized with his winning of the Masterton Trophy after the 1993-94 season. Sadly, a degenerative hip condition forced Neely into a premature retirement. His #8 jersey has been retired by the Bruins, making him the tenth player to have a number retired by the team.

Neely was inducted into the Hockey Hall of Fame in 2005.

Off the ice, Neely's personal family tragedies, with both his parents dying of cancer, have made him very aware of those whose circumstances are less fortunate than his own. Today, Neely remains active in the Cam Neely Foundation run in conjunction with the New England Medical Center, where patients and their families avail themselves of accommodation at the "Neely House" while undergoing cancer treatments.

Neely has also appeared on close friend Denis Leary's series Rescue Me, playing a hockey-playing firefighter who wreaks havoc during a NYPD vs. FDNY game.

Neely also had a cameo appearance in the movie Dumb & Dumber, as the character Sea Bass. Sea Bass was brought back as a smaller cameo role in the film Me, Myself and Irene.