An offensively gifted forward, Vanek played two seasons at Minnesota garnering numerous awards and leading the Golden Gophers to the NCAA Frozen Four title in 2003 before opting to turn pro during the 2004-05 season. In his two seasons of collegiate hockey, Vanek registered 113 points (57-56-113).

In 2004-05, Vanek was named to the AHL's All-Rookie Team, finishing his first professional season with the Rochester Americans with 68 points (42-26-68) while finishing second in the AHL in goal-scoring.

Vanek went on to make his NHL debut with Buffalo during the 2005-06 season. He went on to register a respectable 48 points in 2005-06 and broke out offensively the following season by registering 84 points in 82 games. He also finished an NHL best +47, earning the NHL Plus/Minus Award. In the 2007 off-season, Vanek's rookie contract came to an end and the Edmonton Oilers offered him a seven-year $50 million offer sheet. However the Buffalo Sabres immediately matched the offer, consequently keeping Vanek under contract until the end of the 2013/14 season.

Vanek continued to be Buffalo's most consistent goal scorer, registering 36 goals in 2007-08 and 40 in 2008-09. The prolific Austrian's production dipped in 2009-10, in part due to an upper body injury he suffered early in the year, though he still managed to score 28 times and record 53 points.

In 2010-11, Vanek would once again reach the 30 goal mark, notching 32 to go along with a career-best 41 assists. The following season was much of the same for Vanek. In 78 games for the Sabres the big winger would record 26 goals and 35 assists.

With the NHL mired in a labour stoppage to begin the 2012-13 season, Vanek joined Grazz 99ers of the Austrian Hockey League to start the year. In 11 games for the club he posted five goals and 10 assists.

When play resumed at the NHL level Vanek would rejoin the Buffalo Sabres. Despite missing 10 games during the shortened season, Vanek would once again lead the Sabres in all offensive categories. In 38 games he scored 20 goals and assisted on 21 more for an impressive 41 points.

On October 28, 2013, Vanek's time in Buffalo would come to an end. The big winger was traded to the New York Islanders in exchange for Matt Moulson as well as a first and second round draft pick.

By the trade deadline during the 2013-14 season, it was obvious that the New York Islanders had fallen out of the playoff race. With the focus turned to next year, Vanek was traded once again to the Montreal Canadiens for Sebastian Collberg and a second round draft pick.

In Montreal, Vanek disappointed in the 2014 NHL playoffs where he was only able to post 5 goals and 10 points in 17 games.

At the conclusion of the playoffs, Vanek signed a contract with the Minnesota Wild on July 1, 2014. After two seasons in Minnesota, which included a 21 goal campaign, Vanek was once again a free agent in the summer of 2016. On July 1st he inked a deal with the Detroit Red Wings. Vanek would suit up in 48 games for the club during the 2016-17 season, recording 15 goals and adding 23 assists. On March 1, 2017, the NHL's trade deadline, Vanek was sent to the Florida Panthers in exchange for Dylan McIlrath and a fourth round draft pick.

Vanek would appear in 20 games for the Panthers before becoming a free agent once again in the summer of 2017. On September 1, he signed a deal to join the Vancouver Canucks. He would appear in 61 games for the Canucks, scoring 17 times, before being traded at the NHL trade deadline once again. This time Vanek was sent to the Columbus Blue Jackets in exchange for Tyler Motte and Jussi Jokinen. Vanek finished the season with the Blue Jackets and as a free agent once again the following summer, agreed to a one-year contract to re-join the Detroit Red Wings.