Looper, a right hander, was originally selected by the St. Louis Cardinals in the first round of the 1996 amateur draft with the third overall pick. He made the opening day roster for the Cards in in 1998, posting an 0-1 record in 3.1 innings of relief work through the first nine St. Louis games. He was then sent back to the Memphis Redbirds, the Cardinals PCL Triple A affiliate, with whom he posted a 2-3 record, allowing 43 hits while in 40.1 innings, striking out 43.
Along with Armando Almanza and Pablo Ozuna, Looper was traded to Florida for shortstop Edgar Renteria after the 1998 season. He would make the 1999 opening day roster for the Fish, and end up pitching 72 games in relief in during his official rookie season. He posted a 3-3 record with a 3.80 ERA in 83 innings pitched.
In 2000, Looper led the team with 73 appearances and posted a 5-1 record wiht a 4.41 ERA. Control was an issue for Looper early in his career, as he posted a 1.589 WHIP and only struck out 29 in 67.1 innings pitched. He also saved his first two games for the Marlins.
2001 saw Looper increase his strikeout rate to 52 in 71 innings while dropping his WHIP to 1.310, as he posted a 3-3 record with a 3.55 ERA while again leading the Marlins pitching staff with 71 games.
In 2002, Looper had an added wrinkle added to his resume, as the Marlins made him their primary closer in mid-July. He would post a progressive career best 3.14 ERA while going 2-5 with 13 saves in an NL fifth best 78 appearances and a career best 1.174 WHIP.
2003 would see Looper retain his role as closer for the Marlins, as he saved 28 games and posted a 6-4 record with a 3.68 ERA in 74 games. He would also be a key figure for Florida in their run to their World Series title that year, going 2-0 with one save in eight postseason games.
Just after helping Florida to their second World Championship, Looper was granted free agency. He would go on to play for the New York Mets and the St. Louis Cardinals before going 14-7 in his final Major League season with the Milwaukee Brewers in 2009.
Looper tried out for the Chicago Cubs during spring training in 2011, but voluntarily retired before the start of the season.