Neal played with the Florida Marlins (2001–2003), San Diego Padres (2004), Boston Red Sox (2005), and Colorado Rockies (2005) of Major League Baseball (MLB).

Although bothered by elbow problems throughout his high school career, Neal made a strong impression with a fastball that topped out at 93 miles per hour (150 km/h) and an ERA of 0.92.

[4] In late August the Marlins recalled him to a spot on their expanded roster; Neal made his major league debut on September 3, 2001 in relief against the Chicago Cubs.

On the four transitions between Calgary and Miami, Marlins assistant general manager Jim Fleming commented: "He went back and forth between clubs, and that's a tough way to pitch.

"[6] Neal began 2003 with the Marlins but spent much of the year with the Triple-A Albuquerque Isotopes after a rocky start in April in which his ERA ballooned to 8.38 in nine appearances.

On a return to the team in September his first pitch was hit into the stands in Veterans Stadium for a grand slam by Mike Lieberthal, and Neal finished the year with an 8.14 ERA.

"[8] Assigned to the Portland Beavers, San Diego's Triple-A team, Neal regained his control and added a changeup to his pitching repertoire.

With Neal out of options, the Padres risked losing him had they attempted to send him back to the minors, so they traded him to the Boston Red Sox for outfielder Adam Hyzdu.

In an odd twist of fate Randy Williams, his former teammate in San Diego and with whom he had competed for a spot in the bullpen, had himself been waived by the Padres and then claimed by Colorado.

[12] In retrospect Boston sportswriter Steve Buckley criticized the trade which had brought Neal to the Red Sox, calling it typical of general manager Theo Epstein:"[the] barely-talked-about Blaine Neal-type acquisition.

Mud Hens manager Larry Parrish gave Neal a vote of confidence: "To me, he has enough stuff to get back to the major leagues.