In 2001, Mota made the Expos out of spring training for the first time in his career. On May 12, he had a 1.59 ERA through his first 20 games of the year. However, eight earned runs allowed over his next six games raised his ERA to 4.00. Afterwards, though, he had a 2.08 ERA through his next 12 games. On June 17, he was the winning pitcher when he threw a scoreless inning in a 4–1 victory over Toronto. In his next game, on June 19, he was the losing pitcher when he gave up three runs (only one run was earned) without recording an out in a 4–1 loss to the New York Mets. However, after that 12-game stretch, he gave up five earned runs over his next four games to bring his ERA up to 4.29. On July 13, he was placed on the disabled list for the first time in his career with right shoulder tendinitis. Mota returned at the beginning of September, but he had a 10.57 ERA and two losses in his final 11 games of the year. He finished the season with a 1–3 record and a 5.26 ERA in 53 games.