Holmes was named the Steelers' starting split end coming into training camp. He enjoyed a breakout season in 2007 as he led the Steelers in receiving yards, receiving touchdowns, and emerged as one of the better known deep threats in the NFL. In Week 1 of the season against the Cleveland Browns, Holmes caught a 40-yard touchdown pass from Ben Roethlisberger as they went on to defeat the Browns 34–7. Week 4 in a loss against the Arizona Cardinals, he enjoyed one of the best games in his young pro career as he finished the game with 6 receptions, 128 yards, and 2 touchdown catches. In Week 9, he enjoyed another two touchdown game against the Baltimore Ravens, both touchdowns came in the first half. He finished the game with 4 catches, 110 yards, and two touchdowns. In Week 16, Santonio Holmes amassed the most yards receiving in a game in his career, as he finished the game with 133 yards receiving against the St. Louis Rams. He finished the year with 942 yards receiving and 8 touchdown catches. He led the league in yards per catch.