Branyan began his professional career in the Cleveland Indians minor league system. He made his big league debut with the Indians, on September 26, 1998, and was ranked the Indians' top prospect in 1999 by "Baseball America". Though he demonstrated the ability to hit home runs with Cleveland, his batting average was low. Indians' manager Charlie Manuel suggested in 2002 that Branyan could benefit from more playing time, but he was traded to the Reds for prospect Ben Broussard during the season. Excited to have a "clean slate," as he put it, Branyan hit 16 home runs with the Reds in 2002 but struggled with injuries in the 2003 campaign. Allowed to become a free agent, he spent 2004 in the minor leagues for the Atlanta Braves and Cleveland before Milwaukee picked him up on July 26. In 51 games for the Brewers, Branyan hit 11 home runs. He competed with Wes Helms for the starting spot at third base in 2005 but again battled injuries much of the season. Branyan signed with the Devil Rays in 2006 and spent most of the year on their roster, but he expressed concern at the fact that he was not an everyday player with Tampa Bay. Traded to the Padres in August, he hit what was at the time the longest home run in Petco Park history, measured at 453 feet. He batted .197 for the Padres in 2007 and was released July 28. Branyan spent brief stints with the Phillies and Cardinals that season before becoming a free agent at the end of the year.