Van Slyke earned All-American honors in baseball as a senior at New Hartford Central High school in New Hartford, New York.
He was drafted in the first round (sixth overall pick) of the 1979 Major League Baseball amateur draft by the St. Louis Cardinals. Called up from the AAA Louisville Redbirds, he made his Major League debut with the Cardinals on June 17, 1983, collecting a double, a run batted in (RBI) and making three putouts in the outfield without an error.
In 1985, he was one of five Cardinals to steal at least 30 bases. He stole 34 that season, part of the "Whiteyball" era.
The first two years of his career Van Slyke played first base, third base and all three outfield positions. He mostly played right field the next two years on the strength of his throwing arm, occasionally platooning with Tito Landrum, sometimes substituting for Willie McGee in center field. On September 21, 1986, he hit a rare inside-the-park home run. During spring training 1987, he was traded to the Pittsburgh Pirates along with left-handed hitting catcher Mike LaValliere and minor league pitcher Mike Dunne for catcher Tony Peña. The trade occurred on April 1, with Van Slyke initially believing that it was an April Fools' Day joke. In Pittsburgh, he mostly played center field alongside stars Barry Bonds and Bobby Bonilla.
During the 1991 Gulf War, when the MLB decreed all players would wear both the Canadian and U.S. flags on their batting helmets as a patriotic gesture, Van Slyke scraped the Maple Leaf off his helmet, stating "I guess the people in Quebec won't be upset because the last time we were there they booed [the Canadian] Nation Anthem". MLB Commissioner Fay Vincent ordered that the Canadian flag decal be reinserted onto the helmet.
Once Van Slyke became a full-time outfielder, he showed off one of the most accurate and powerful throwing arms in the majors, so much that the "Slyke Zone" was established at Three Rivers Stadium. From 1985 to 1994, he was frequently among the league leaders in outfield assists. From 1985 to 1988, he posted seasons of 13, 10, 11, and 12 assists, respectively. As center fielder for the Pirates, he won five consecutive Gold Gloves from 1988 to 1992.
Van Slyke played for four different teams in his career: the St. Louis Cardinals (1983–1986), Pittsburgh Pirates (1987–1994), Baltimore Orioles (1995), and Philadelphia Phillies (1995). He played his final game on October 1, 1995. In his 13-year career, Van Slyke appeared in three All-Star games (1988, 1992, 1993), won five Gold Glove Awards, two Silver Slugger Awards, and ranked in the top 10 in many offensive categories in varying seasons.
Prior to the 2006 season, Van Slyke was named first base coach for the Detroit Tigers by manager Jim Leyland, under whom he had played in Pittsburgh. Van Slyke served in that capacity on Leyland's staff for four years through the 2009 season.
When Lloyd McClendon was named the Seattle Mariners' manager prior to the 2014 season, Van Slyke was hired to be the team's first base coach. He also worked as the assistant hitting coach and outfield instructor through the 2015 season.June 5, 1979: Drafted by the St. Louis Cardinals in the first round (6th pick) of the 1979 amateur draft.
April 1, 1987: Traded by the St. Louis Cardinals with Mike Dunne and Mike LaValliere to the Pittsburgh Pirates for Tony Peña.
October 21, 1994: Granted free agency.
April 21, 1995: Signed as a free agent with the Baltimore Orioles.
June 18, 1995: Traded by the Baltimore Orioles to the Philadelphia Phillies for Gene Harris.
November 3, 1995: Granted free agency.
# = MLB All-Star Game selection
Van Slyke became eligible for the National Baseball Hall of Fame in 2001. 75% of the vote was necessary for induction, and 5% was necessary to stay on the ballot. Of the 32 total candidates, Van Slyke received no votes and was eliminated from future BBWAA voting.
Having retired from baseball, Van Slyke has begun pursuing a career as an author, focusing on books centered on baseball. In 2009, he authored Tiger Confidential: The Untold Inside Story of the 2008 Season (with co-author Jim Hawkins). In July 2010, he published The Curse: Cubs Win! Cubs Win! Or Do They? (with co-author Rob Rains), a book in the subgenre sports fiction about the Chicago Cubs finally breaking their one hundred year curse and playing in the World Series.
Van Slyke has four sons, three of whom played college or professional sports. Scott Van Slyke plays for the Los Angeles Dodgers; Jared Van Slyke was a defensive back on the University of Michigan football team; and A. J. Van Slyke played baseball for the University of Kansas and for four seasons in the St. Louis Cardinals' minor league system.
He attended New Hartford Central High School in New Hartford, New York, Class of 1979. His father was the school's principal.