Zetterberg started his youth league career playing games for the Njurunda Sports Club, as did Fredrik Modin.

[4] Zetterberg caught the attention of the Red Wings' Assistant General Manager Jim Nill and Director of European Scouting Håkan Andersson during a tournament in Finland.

Zetterberg finished the season as runner-up for the Calder Memorial Trophy as rookie of the year behind St. Louis Blues defenceman Barret Jackman.

[6] Due to the owners' lockout the next season, Zetterberg returned to Sweden to play for Timrå IK in 2004–05, leading the Elitserien in scoring with 50 points in 50 games.

He enjoyed his second best statistical season in 2005–06, tallying 39 goals and 85 points, second in team-scoring to Pavel Datsyuk in a lineup which included Zetterberg and teammates Tomas Holmström, Mikael Samuelsson, Nicklas Lidström, and Niklas Kronwall.

Zetterberg began the 2007–08 season with a 16-game point-scoring streak, breaking the record of 14 games set by former Red Wing Norm Ullman in 1960.

[12] Despite missing time due to injury, Zetterberg recorded a career-year with personal bests of 43 goals, 49 assists and 92 points in 75 games.

At the end of the season, Zetterberg was also up for the Frank J. Selke Trophy as the best defensive forward, but finished as a runner-up to Datsyuk.

Despite a slow start to the 2009–10 NHL Season, Zetterberg's play quickly improved, and he recorded the fourth hat trick of his career on 14 November against the Anaheim Ducks, scoring three goals in the third period of Detroit's 7–4 victory.

However, he sustained another back injury during the 2014 Winter Olympics and underwent surgery, causing him to miss an estimated two months of the season while the Red Wings pursued a berth in the NHL playoffs for the 23rd straight year.

[17] Zetterberg returned for the final two games of the 2014 Stanley Cup playoffs as the Red Wings were eliminated in the Eastern Conference Quarterfinals by the Boston Bruins.

[23] On 14 September 2018, Red Wings general manager Ken Holland announced that due to a degenerative back condition, Zetterberg would be unable to continue with his NHL career.

Zetterberg won a gold medal at the 2006 Winter Olympics in Turin and then again at the 2006 IIHF World Championship in Riga, playing a part in the international sweep.

Zetterberg along with teammates and fellow Swedes Niklas Kronwall and Mikael Samuelsson are the fastest to accomplish this feat, requiring only two years, three months and ten days.

[28] Zetterberg goes by the nicknames of "Zäta" (pronounced "Zaeta," which means "Z" in Swedish) and "Hank," an anglicized shortening of Henrik that is used by his Red Wings teammates.

[31] Zetterberg served several months in the Swedish Army when he was 17 years old—a rare thing among NHL players—as Sweden at that time had a conscription policy.

The videos centre around a bumbling Henrik Zetterberg look-alike (played by Hawkins) and were positioned as spec commercial spots for the NHL and their affiliates.