Branyan was first called up to the Cleveland Indians in . In his major league debut on September 26, 1998, Branyan went 0-for-4. The next season, , Branyan played 11 games with Cleveland, batting .211 with one home run and six RBIs. Branyan got his first hit (also his first home run) on July 23, 1999, off of David Cone, a pitcher for the New York Yankees. In , Branyan continued his struggles, hitting .238 with 16 homers. After the 1999 season, "Baseball America" named Branyan as the Indians top prospect. His home-run prowess caused "USA Today" to compare him with Mark McGwire. On June 1, 2000, he hit two home runs in one game, the first two home run game of his career. In , an injury to Travis Fryman moved Branyan to third for a good part of the season. He again had a poor average, batting .232, with 20 home runs. In , manager Charlie Manuel wanted Branyan to succeed Fryman full-time, though he was primarily used as a utility player throughout the season. Manuel stated that Branyan should be an everyday player saying, "He's definitely not a guy you want sitting on the bench, because of the timing in his swing." In spring training, Branyan was promised that he would be an everyday player. He hit .205 with just 8 homers before he was traded to Cincinnati for prospect Ben Broussard.