Stam played for several European clubs including PSV Eindhoven, Manchester United, Lazio, Milan and Ajax before retiring in October 2007.

As well as winning numerous club trophies including an Eredivisie, a Coppa Italia, an Intercontinental Cup and three Premier League titles, he won several personal awards including being voted the best defender in both the 1998–99 and 1999–2000 UEFA Champions Leagues as well as being in three consecutive PFA Team of the Year sides from 1999 to 2001.

On 15 August 1992, Stam made his professional debut for FC Zwolle in a 1–1 draw against SC Heracles in the Eerste Divisie.

In April 1998, Stam became the then most expensive defender in history when Manchester United bought him on a five-year contract for £10.6 million.

[10] In the 1999 UEFA Champions League final, Stam's centre-back partner Ronny Johnsen conceded a free kick on the edge of the penalty area when he brought down Bayern Munich's Carsten Jancker in the first few minutes.

Stam made numerous statements in the book about his views on opposing players, and alleged that Ferguson's approach to buy him was done without the permission of PSV.

[12] Later, Simon Kuper reported that contrary to initial belief, Ferguson had noticed that Stam's tackling numbers were declining and simply assumed the defender was past his playing peak.

[14] In 2007, however, Ferguson described the decision to sell Stam as an error: "At the time he had just come back from an achilles injury and we thought he had just lost a little bit.

He reached his second Champions League final with the Rossoneri in 2005, but was a runner-up after his team was defeated by Liverpool in a penalty shoot-out.

[20] On 30 January 2006, it was announced that he would return to the Eredivisie and play for Ajax, where he signed a two-year contract for a €2.5 million transfer fee.

He was not initially chosen for UEFA Euro 1996, but was later added to the squad after an injury ruled out Frank de Boer; he did not however make any appearances at the tournament.

Stam missed his attempt in the penalty shoot-out in the semi-finals, hitting the ball over the bar in a defeat against Italy.

He was known for possessing "a rare combination of speed, strength and ball-playing ability",[25] as well as an excellent positional sense and a powerful shot.

"[41][42] On 21 May 2020, Major League Soccer club FC Cincinnati announced that Stam would succeed interim manager Yoann Damet.

[43] On 15 July, he won 1–0 on his debut against an Atlanta United FC side managed by his former international teammate Frank de Boer.

[45] In February 2024, Stam was appointed manager at seventh-tier DOS Kampen, his hometown amateur club where he had begun playing more than three decades earlier.

[49] His first daughter's birth was induced two weeks early, to come between the 1998 World Cup and pre-season training for Manchester United.