The 40-year-old Atlanta captain made the announcement less than a week after the Thrashers, the last of the five clubs he played for, were swept in the first round of playoffs by the New York Rangers.
"I'm very comfortable with my decision," Mellanby said on a conference call. "I feel I've given what I have and I don't feel either physically or mentally at this point that I can do it again."
The Montreal native, the son of former Hockey Night in Canada executive producer Ralph Mellanby, entered the league with the Philadelphia Flyers in 1986 and played for Edmonton, Florida and St. Louis before spending his last two seasons with the Thrashers.
In 1,431 regular-season games - tied for 17th on the NHL's career list - the muscular right-winger had 364 goals, 476 assists and 2,479 penalty minutes. He also appeared in 136 playoff games, scoring 24 goals and adding 29 assists.
A regret is that, although he went to the Stanley Cup final with Philadelphia in 1987 and Florida in 1996, he never won the ultimate prize.
"I'd be lying if I said the Stanley Cup wasn't what pushed me to keep playing year after year," he said. "It's disappointing, but it's so tough now.
"Since I came in, the league's gone from 21 to 30 teams and that makes it even tougher. There's a lot of good teams that don't even get into the playoffs."
Mellanby is known for producing the "rat trick" during the memorable campaign when expansion Florida, in only its third NHL season, reached the Cup final.
It started when Mellanby killed a rat with his stick in the Panthers' dressing room before their home opener on Oct. 8, 1995, then went out and scored two goals. Goalie John Vanbiesbrouck called it a "rat trick."
For the rest of the season, fans threw plastic rats onto the ice whenever a Panther scored - all the way through to their Cup final loss to the Colorado Avalanche. The league banned the practice the following season because it took too long to clear the ice.
"My whole experience in Florida was huge in my career," he said.
Mellanby was drafted out of junior B hockey in Toronto in the second round by Philadelphia in 1984 and played two seasons at the University of Wisconsin before joining the Flyers for two games in the 1985-86 season.
He helped Philadelphia reach the Cup final against Edmonton in his first full season, then established himself as a productive power winger until a nasty incident in a bar fight nearly ended his career.
Mellanby needed surgery to repair a severed nerve and artery and cut five tendons in his left arm when he was slashed with a broken bottle after coming to a friend's defence during a skirmish in a bar in Gravenhurst, Ont., on Aug. 20, 1989.
The injury caused him to miss the start of the 1989-90 season and bothered him throughout the season, when he had only six goals in 57 games. He received a $750,000 insurance settlement from the incident.
In 1991, he went to Edmonton in a multi-player deal that brought Jari Kurri to the Flyers, but after two seasons, was left unprotected in the 1993 expansion draft and was claimed by Florida. The Panthers' general manager at the time was Bob Clarke, who had drafted him for the Flyers nine years earlier.
"At 27, I had some decent years in the league and being left available for expansion was not something I anticipated," he said. "But (Oilers' GM) Glen Sather did tell me if he had a good team at that point he would have kept me, but they were going through a rebuilding process.
"Going to Florida, I was ready to take another step as a leader. I was put into a position to produce offensively and put in quality ice time."
Mellanby had his best years in Florida, scoring 30 goals in 1993-94 and career highs of 32 goals and 70 points in 1995-96.
But back and head injuries hampered him in four of the next five seasons, during which he was traded to St. Louis, where he played four seasons.
He signed as a free agent with Atlanta in 2004.
Thrashers' GM Don Waddell praised Mellanby's leadership as an important part of the team's evolution. The Thrashers made the playoffs this season for the first time in their seven-year existence.
"He has helped our organzation grow and has played an important role in helping to shape a culture that will allow the Thrashers to be successful for many years to come," Waddell said in a statement.
In 2002, Mellanby became the first NHL player to score 300 career goals without ever scoring a hat-trick. In 2003, he got his first hat-trick in his 1,209th career game.