[4] An accomplished box lacrosse player, Nieuwendyk led the Whitby Warriors to the 1984 Minto Cup national junior championship before focusing exclusively on hockey.

His brother Gil was a box lacrosse player,[9] while his uncle Ed Kea and cousin Jeff Beukeboom also played in the National Hockey League (NHL).

Eligible for the 1984 NHL Entry Draft but unselected, he chose to attend Cornell University where he played hockey and lacrosse for the Big Red.

[7][11] He was named the Eastern College Athletic Conference (ECAC) hockey rookie of the year in 1984–85 after scoring 39 points in 23 games.

[16] At the 1985 NHL Entry Draft, the Calgary Flames selected him in the second round, 27th overall, with a pick obtained that day in a trade with the Minnesota North Stars for Kent Nilsson.

[17] The disappointment in Calgary over the trade of Nilsson resulted in some criticism of Nieuwendyk's selection, famously leading to a local newspaper to question the moves with the headline "Joe Who?

[20] Once his junior season at Cornell ended, Nieuwendyk joined the national team for five games before turning professional with the Flames.

In the clinching game against the Montreal Canadiens, he set up Lanny McDonald's final NHL goal with a quick pass after receiving the puck from Håkan Loob.

[16] He missed he first 11 games of the 1991–92 NHL season after suffering a knee injury during a summer evaluation camp for the 1991 Canada Cup.

[27] He refused an offer of a three-year, $6 million contract from the Flames, and as the dispute dragged on, chose not to join the team when the season began.

[28] He remained a holdout until December 19, 1995, when the Flames traded him to the Dallas Stars in exchange for Jarome Iginla and Corey Millen.

[30] Bob Gainey, the team's general manager, hoped that the acquisition of Nieuwendyk would help the franchise, which had relocated from Minnesota three years previous, establish its place in Dallas.

In the opening game of the Stars' first-round series against the San Jose Sharks, he suffered a torn ACL as a result of a check by Bryan Marchment.

[31] The injury required two knee surgeries to repair and six months to heal, which caused him to miss the beginning of the 1998–99 NHL season.

[37] Two months later, on March 19, 2002, he was traded to the Devils, along with Jamie Langenbrunner, in exchange for Jason Arnott, Randy McKay and a first round selection in the 2002 NHL Entry Draft.

[38] He scored 11 points in 14 regular season games for the Devils following the trade,[21] but New Jersey was eliminated in the first round of the 2002 Stanley Cup playoffs by the Carolina Hurricanes.

He signed another one-year deal for 2004–05, but the season was cancelled due to a labour dispute that was feared would mark the end of his 38-year-old career.

[48] One year later, he joined the senior national team for the Calgary Cup, a four-team exhibition tournament that served as a preview event for the 1988 Winter Olympics.

[51] He joined the senior team again for the 1990 Men's World Ice Hockey Championships, but appeared in only one game after suffering a knee injury.

[53] He scored two goals and three assists in six games,[21] but was one of several Canadian players stopped by Czech goaltender Dominik Hašek in a shootout loss in the semifinals.

"[31] He was an offensive centre in Calgary and power play specialist, able to withstand the physical punishment required to stand in front of the net and battle defencemen for the puck.

Devils' general manager Lou Lamoriello praised his impact both on and off the ice: "Certainly (the tangibles were) the quality player he was even at that time, how good he was defensively as well as always finding a way to get big goals.

[60] Remaining in hockey following the end of his playing career, Nieuwendyk joined the Florida Panthers' front office as a consultant to general manager Jacques Martin in 2007.

[61] He left the Panthers after one year to join the Maple Leafs as special assistant to general manager Cliff Fletcher in 2008.

[64] Among his decisions in his first two seasons as general manager was to allow popular former captain Mike Modano to leave the organization after 22 years with the franchise in 2010.

In 1995, while a member of the Flames, Nieuwendyk won the King Clancy Memorial Trophy given annually to the player "who best exemplifies leadership qualities on and off the ice and who has made a significant humanitarian contribution to his community".

He was honoured by the league for his contributions to the Society for the Prevention of Cruelty to Animals (SPCA), and was a spokesman and honorary chairman of the Foothills Hospital Foundation.