He played in Major League Baseball (MLB) for the Tampa Bay Devil Rays/Rays, Oakland Athletics, Kansas City Royals, and Chicago Cubs.

A versatile defender and a switch-hitter with a high walk rate,[1] he played roughly half his innings at second base, and spent significant time at shortstop and various outfield positions.

[6] Zobrist played baseball starting when he was eight years old; he and his friends built their own wiffle ball field behind his house.

Zobrist planned to attend Calvary Bible College in Kansas City, Missouri, but his high school coach encouraged him to spend $50 to participate in an annual summer event that showcased seniors in Peoria, Illinois.

In 2002 he was named to both the all-CCAC and all-Region VII First Teams, and received NAIA Honorable Mention All-America status.

[9] He transferred to Dallas Baptist University for his senior year, where he played shortstop and batted .378 with a .590 slugging percentage.

With right-handed pitcher Mitch Talbot, Zobrist was traded to the Tampa Bay Rays for first baseman/designated hitter Aubrey Huff and cash on July 12, 2006.

"He added the power component", Rays executive vice president Andrew Friedman said, "He became a lot more physical.

His versatility was showcased during Game 3 of the 2008 World Series against the National League champion Philadelphia Phillies when he came in as part of a double switch to play right field.

Zobrist was placed in right field for the beginning of the 2009 season, and was made the starting second baseman after teammate Akinori Iwamura was injured.

[17] On April 23, 2010, Zobrist and the Rays agreed to a three-year contract extension through the 2013 season, with a team option for 2014 and 2015, a deal potentially worth $30 million.

[19] On April 28, 2011, Zobrist collected a Tampa Bay Rays record eight RBIs in a 15–3 rout of the Minnesota Twins.

[23] On April 8, 2013, Zobrist became the strikeout victim on a disputed call that led to Joe Nathan's 300th career save.

[25] On January 10, 2015, Zobrist was traded to the Oakland Athletics with teammate Yunel Escobar in exchange for John Jaso, Daniel Robertson, and Boog Powell.

On April 25, 2015, it was revealed that Zobrist had a torn medial meniscus in his left knee, putting him on the 15-day disabled list.

[30] The Royals won the AL Central Division and played the Houston Astros for the ALDS with Zobrist starting in all five games.

The Royals advanced to the World Series after defeating the Toronto Blue Jays in six games to become the American League Champions.

[36] He became the eighth player in Major League history to win consecutive World Series championships on different teams.

[39] In 2019, Zobrist started the season playing in 26 games before being placed on the restricted list on May 6 to deal with a family matter.

Following rumors throughout the next months, Zobrist announced his return in late July 2019, and began rehab assignments with the South Bend Cubs and Myrtle Beach Pelicans.

[55] St. Pete Times writer Marc Topkin wrote Zobrist "doesn't judge or proselytize, refraining from forcing his beliefs on anyone, though willing to get involved if asked.