Surhoff attended Rye High School in Westchester, New York and hit a monstrous home run as a visitor at Somers High School which cleared route 139 and hit the firehouse. The home run was dubbed "The Killer," and is infamous in high school baseball lore as it bounced off the firehouse and killed a small squirrel. The spot the home run landed is still marked. After high school he attended the University of North Carolina at Chapel Hill, where he was honored as the 1985 ACC Male Athlete of the Year, and played on the very first (1984) U.S. Olympic baseball team. He was a two-time first team All-American at UNC and his career batting average of .392 was a school record until Dustin Ackley set the mark at .412 in 2009.
He was selected by the Brewers with the first overall pick of the 1985 amateur draft. Surhoff was a very versatile player, having appeared at every position except pitcher over the course of his career. He had 2,326 hits and 1,153 RBI in his career. Although always a consistent hitter, having hit over .280 in 12 of his 19 seasons, Surhoff's finest season was his 1999 campaign with the Orioles, in which he led the American League in at-bats (673), ranked second in hits (207), was selected to the American League All-Star team, and ultimately won Most Valuable Oriole honors for the season, becoming one of five players to get 200 or more hits in a season for the team. He also participated in the Home Run Derby. In other notable seasons, he finished sixth in the AL in doubles in 1993 with the Brewers and finished fifth in batting average in the AL with the Brewers in 1995 with a .320 average.
In 2007, Surhoff was elected to the Orioles Hall of Fame, with the official induction ceremony occurring before the start of the Orioles–Twins game on August 25, 2007, at Oriole Park at Camden Yards.
Surhoff lives in Cockeysville, Maryland with his wife Polly and their four children. He is the president of Pathfinders for Autism, a Hunt Valley support group for families with autistic children. Surhoff's son, Mason, is autistic.
Surhoff is the uncle of former UNC third-team All-American pitcher Brian Moran, and current Houston Astros minor league third baseman Colin Moran. In 2008, 2009 and 2012 Surhoff was a spring training instructor for the Baltimore Orioles.