Peluso played in the NHL from 1990 until 1998 with the Chicago Blackhawks, Ottawa Senators, New Jersey Devils, St. Louis Blues, and Calgary Flames.

[2][3] The NCAA did not allow fighting and Peluso became the Seawolves' all-time scoring leader at defense, and set records for assists and points in a season by a defenseman.

Upon joining the Hawks, he was switched to forward and encouraged to fight in order to stay in the lineup by coach Mike Keenan.

[5] He was assigned to Chicago's affiliate, the Indianapolis Ice of the International Hockey League (IHL), where under coach Darryl Sutter, he was taught how to be a role player.

[11] He scored his first NHL goal on October 16 on Tim Cheveldae, putting in a rebound off a shot from Troy Murray in a 3–2 loss to the Detroit Red Wings.

[14] He returned to Chicago on December 28[15] On March 17, 1991, in a violent game versus the St. Louis Blues, Peluso was one of three Blackhawk goalscorers to take a 4–2 lead.

[16] Peluso and Kelly Chase of the Blues were suspended for ten games and received a $10,000 fine for leaving the bench for fighting.

[25][26] Peluso played a key role in the Blackhawks run to the Stanley Cup finals that playoffs where they lost to the Pittsburgh Penguins.

[37] He registered his first point for the Devils in the following game on October 8, assisting on Scott Stevens' opening goal in the first period of a 6–3 win over the Washington Capitals.

[39][40] During the lockout-shortened 1994–95 NHL season he was an integral part of the infamous "Crash Line" with Randy McKay and Bobby Holík, a fourth-line combination whose energy and timely goal-scoring.

[43][44] Peluso missed 14 games due to the hit by Darius Kasparaitis of the Islanders on his already injured left leg, returning on April 2 versus the New York Rangers.

[47] Peluso returned to the Devils for the beginning of the 1996–97 season, with Denis Pederson replacing Holík on the fourth line.

[49] He made his first appearance for the Blues on November 27 in a 3–2 victory over the Mighty Ducks of Anaheim, playing on a line with Geoff Courtnall and Peter Zezel.

[56] However, the Rangers chose to leave him unprotected in the waiver draft on September 28 and Peluso was selected by the Calgary Flames.

[59] Peluso began to miss time with a chronic neck injury and received a diagnosis of spinal stenosis.

On December 18, 1993, while playing for the New Jersey Devils in a game against the Quebec Nordiques, Peluso was injured in a fight against Tony Twist.

[62] Peluso was later traded to the St. Louis Blues during the 1996–97 NHL season before finishing his professional career with the Calgary Flames the following year.

In 2012, after years of suffering from seizures, dementia, memory loss, anxiety and depression, Peluso filed for workers' compensation in California, naming the last four teams he had played for in his NHL career (he suited up for the Ottawa Senators prior to sustaining the concussion) as defendants.

[66] Several months passed with no resolution in the matter and in January 2019 Peluso sued the New Jersey Devils, former general manager Lou Lamoriello and doctors Marvin Ruderman, Len Jaffe and Barry Fisher.