Héctor Santiago, a left-handed pitcher, began his Major League Baseball career with the Chicago White Sox. Drafted in the 30th round of the 2006 MLB Draft, Santiago worked his way through the minor leagues, making his MLB debut on July 6, 2011. Known for his unique pitching style, Santiago utilized a screwball, a rare pitch in modern baseball, which helped him stand out among his peers.

During his time with the White Sox, Santiago transitioned between starting and relieving roles. In 2012, he was named the team's closer for a brief period, showcasing his adaptability on the mound. The following year, he moved into the starting rotation, where he demonstrated his ability to handle a heavier workload. Santiago's tenure with the White Sox concluded after the 2013 season when he was traded to the Los Angeles Angels as part of a three-team deal.

With the Angels, Santiago solidified his role as a starting pitcher. In 2015, he earned his first and only All-Star selection, a testament to his performance during the first half of the season. That year, he posted a 3.59 ERA over 180.2 innings, contributing significantly to the Angels' pitching staff. Santiago's time with the Angels lasted until mid-2016 when he was traded to the Minnesota Twins.

Santiago's stint with the Twins was marred by injuries, which affected his performance and limited his playing time. Despite these setbacks, he continued to pitch for the Twins until the end of the 2017 season. In 2018, Santiago returned to the White Sox on a minor league deal, eventually making it back to the majors. He split his time between starting and relieving, providing depth to the pitching staff.

The following year, Santiago signed with the New York Mets, where he primarily served as a reliever. His tenure with the Mets was brief, and he was released in August 2019. Santiago continued to pursue opportunities in professional baseball, signing a minor league contract with the Detroit Tigers in 2020. However, the COVID-19 pandemic led to the cancellation of the minor league season, and Santiago did not appear in any games for the Tigers.

In 2021, Santiago signed a minor league deal with the Seattle Mariners. He was called up to the majors in June and made headlines when he became the first player ejected under MLB's new foreign substance policy. Despite this controversy, Santiago continued to pitch for the Mariners, providing veteran experience to their bullpen.