He played seven seasons in Major League Baseball (MLB) for the Houston Astros (2000-2001), Milwaukee Brewers (2002-2003), San Francisco Giants (2004), New York Yankees (2005), and Atlanta Braves (2006).

Wayne began his professional career with the Los Angeles farm team the Yakima Bears in 1996, where he went 1–0 with 1 save and a 2.52 ERA.

In 1998, playing with the Vero Beach Dodgers, Franklin earned a career-high 9 wins and he also notched 10 saves and a 3.53 ERA in 86.2 innings pitched.

Franklin began the 2000 season with the AAA New Orleans Zephyrs, but was called up after 48 games when he put up a 3–3 record with a 3.63 ERA.

In 2001, Wayne was on the Houston Opening Day roster and made 11 relief outings, but was sent down to the Zephyrs on May 5 after putting up a 6.75 earned run average.

On September 3, he was traded to the Milwaukee Brewers along with Keith Ginter to complete an earlier deal involving Mark Loretta.

After going 10–13 with a 5.50 earned run average and a career-high 116 strikeouts for the Brewers in 2003, Franklin was traded to the San Francisco Giants along with Leo Estrella, for Carlos Villanueva and Glenn Woolard on March 30, 2004.

Franklin was converted back to a reliever in 2004 for San Francisco after having led the league in home runs allowed the year before, going 2–1 with a 6.39 ERA and 40 strikeouts.

Franklin signed a minor league contract with the Tampa Bay Devil Rays on January 11, 2006, and was invited to spring training.

On December 5, 2006, Franklin signed a minor league contract with the Kansas City Royals and was invited to spring training.

Franklin has also spent time in recent years as a pitching coach for San Francisco State, Menlo and Holy Names.