Parise played midget AAA hockey for four seasons for the Shattuck-St. Mary’s Sabres in Faribault, Minnesota, where his father J. P. worked in the hockey program. During his final two years (2000–01 and 2001–02) at Shattuck-St. Mary’s, he scored 146 goals and 194 assists in 125 games. While playing for the Sabres, Parise twice participated in the Mac’s AAA Hockey Tournament held in Calgary, Alberta. In 2000 and 2001, Parise was named the tournament Most Valuable Player (MVP) as well as being named to the tournament All-Star Team. He was the top scorer at the 2001 tournament. After his senior year at Shattuck-St. Mary’s, Parise was named the school’s Best All-Around Athlete.

After his sophomore season at UND, Parise chose to forgo his final two years of NCAA eligibility to sign a professional contract with the New Jersey Devils. He signed an entry-level contract with the Devils on March 29, 2004. Due to the 2004–05 NHL lockout, Parise spent his first professional season in the American Hockey League (AHL) with the Albany River Rats. In his first professional season, Parise scored 18 goals and added 40 assists. He was chosen to play in the 2004–05 AHL All-Star Game.

In 2005 and 2007, Parise played for the United States at the World Hockey Championships, although he did not suit up for the full slate of games in either event. In 2008, Parise served as an alternate captain for the American team at the World Championships. He was named Team USA’s Player of the Game against Germany during this tournament, and he was also selected as one of the team’s Top Three Players at the end of the tournament by the coaching staff.

To open the following season, Parise set a franchise record for scoring the quickest season-opening goal, 26 seconds into the first game. For the season, he nearly doubled his scoring output of the previous season, totaling 62 points. Parise was chosen to play in the NHL YoungStars Game during the All-Star weekend, where he scored two goals and four assists and was named the game’s MVP. Heading into the 2007–08 season, Parise and the Devils agreed to terms on a new, four-year contract on August 1, 2007. Parise led the Devils in scoring during the 2007–08 season with 65 points. On November 30, 2007, in a game against the Montreal Canadiens, Parise got his first NHL natural hat-trick.

On October 3, 2008, Parise was named an alternate captain for the Devils. He had a breakout season during his fourth year in the NHL, which saw the Devils increase their scoring output by nearly half a goal per game, breaking away from the team’s image as a mostly defensive team. While playing in all 82 games, Parise scored 45 goals and added 49 assists for 94 points. Parise finished fifth overall in NHL scoring, and was third in goal scoring, behind only Alexander Ovechkin and Jeff Carter. During the season, Parise was selected to represent the Eastern Conference at the 2009 All-Star Game. After the season, Parise was chosen as one of three nominees for the Lady Byng Memorial Trophy, awarded to the NHL’s most sportsmanlike player. He was also chosen to the NHL’s Second All-Star Team, and named the Devils’ team MVP.

During the 2009–10 season, Parise played in 81 games for the Devils, finishing with 38 goals and 44 assists. Parise struggled at times, going 12 games without scoring at one point before recording two goals against the Atlanta Thrashers on December 28, 2009. During the playoffs, Parise and the Devils were eliminated in the Eastern Conference Quarter-finals by the Philadelphia Flyers in five games. Parise scored one goal and added three assists in the five playoff games. At the end of the season, he was selected as the Devils’ team MVP for the second year in a row.

On January 1, 2010, Parise was named to the 2010 Men’s Olympic Hockey Team, and was later named as one of the team’s alternate captains. Parise scored both of Team USA’s goals in 2–0 quarter-final win over Switzerland. In the final against Canada, Parise scored a game-tying goal with 24 seconds left in the third period to send the game into overtime, although Parise and his teammates had to settle for the silver medal after a Sidney Crosby goal during overtime. For the tournament, Parise finished third in the tournament in scoring, and he was named to the Olympic All-Star team with countrymen Ryan Miller and Brian Rafalski. In 2014, Parise was again selected to represent his country at the Olympics, and was given the added responsibility of serving as team captain. Parise and the United States capped off their 2014 Olympic campaign with a 5–0 loss to Finland in the bronze medal game.

In November of the 2010–11 season, Parise tore the meniscus in his right knee, underwent surgery and was deemed to be likely out for the remainder of the season. On March 2, 2011, Parise was cleared to start skating and returned to play on April 2, the same night the Devils were mathematically eliminated from playoff contention.

On July 29, 2011, Parise signed a one-year contract worth $6 million with the Devils. On October 5, 2011, the Devils named him captain. Parise became the second captain in Devils history (the other being Scott Stevens) to lead them to the Stanley Cup Finals. The Devils were down 0–3 in the series before finally losing in six games at the hands of the Los Angeles Kings.

On July 4, 2012, Parise left the Devils’ organization to sign with his hometown Minnesota Wild. Parise noted that his parents played a role in him signing with the Wild, stating “When I made the decision they were real excited as well. That played a big part. I grew up here, I love coming back here in the summers and I thought ‘We enjoy it here so much it would be great to be here year round.'” Parise’s father, J.P., once captained the Minnesota North Stars. The Wild signed Parise, as well as fellow free agent Ryan Suter, to identical 13-year, $98 million contracts. Parise chose to wear No. 11, the same number his father wore as a North Star; Parise’s No. 9 he wore with the Devils was already worn by team captain Mikko Koivu. On July 9, both Parise and Suter were named alternate captains.

On March 20, 2014, Parise returned to the Prudential Center for the first time since leaving the Devils during the 2012 off-season. Parise was booed every time he skated with the puck, especially when his name was announced for a goal. The Wild ended up losing the game 4-3 in overtime.

On November 6, 2014, it was announced that Parise was out “indefinitely” due to a concussion he suffered two days earlier during a 4–1 loss to the Pittsburgh Penguins. Five games later, on November 16, he returned to the Wild lineup. He finished the season with 62 points.

Parise resides in Edina, Minnesota. He is married to his college sweetheart Alisha Woods and they had twins together in 2014. Parise’s parents, former NHL player and coach J. P. and Donna, lived in Prior Lake, Minnesota. Parise’s father died on January 7, 2015. Parise’s father was a Franco-Ontarian from Smooth Rock Falls in Northern Ontario, and was diagnosed with cancer during the Winter Olympics. Zach was born during his father’s tenure as assistant coach of the Minnesota North Stars.

On October 23, 2016, Parise scored 2 goals to earn his 300th goal in his career, in a loss against the New York Islanders.

In 2016, Parise was selected to play for Team USA at the 2016 World Cup of Hockey.

Parise played his 1000th Career NHL Game on February 7th 2020 in an away game against the Dallas Stars.