In December 2006 Marquis signed a three-year contract with the Chicago Cubs worth $21 million. With the Cubs, he wore his favorite # 21, the number formerly worn by ex-Cubs slugger Sammy Sosa, who coincidentally hit his 600th home run against Marquis. This caused some concern, due to Sosa's accomplishments with the Cubs, including his status as the Cubs' all-time home run leader. On May 9, Marquis completed a three-hit shutout against the Pittsburgh Pirates, defeating them 1–0. He had a perfect game going into the 6th inning, retiring the first 16 batters he faced, but Pirates shortstop Don Kelly broke it up with a single. The game took only two hours and six minutes. Marquis struck out five, and needed only 109 pitches to complete the game. "His ball was diving and darting. He was awesome," said teammate Jacque Jones. The win improved Marquis' record to 5–1, and dropped his ERA to 1.70, 3rd-best in the NL. After the game, Marquis highlighted his consistency as being the key to his turnaround. "My delivery is as consistent as it's ever been. I feel like I'm repeating the same delivery over and over again and that's the reason, I really believe, for the success." In 2007 Marquis was 12–9, with a 4.60 ERA. He was tied for 2nd in the league in shutouts (1), was 5th in the league in hit batsmen (13), had the 5th-lowest batting average in the NL of balls hit into play against him (.280), and had the 8th-highest ground ball percentage (49.5%). He kept batters to a .229 batting average in games that were late and close. On March 24, 2008, it was announced he would be the Cubs' fifth starter for the 2008 season. Historically, Marquis' numbers during the second half of the season were not as good as his numbers during the first half, but thanks to smart managing by Lou Piniella, Marquis and Rich Harden, newly acquired from the Oakland Athletics on July 8, rotated their starts for a time, and Marquis posted a winning month of August, going 3–1 with a 3.90 ERA. It was his second-lowest ERA after a 3.81 ERA in July. He finished the season 11–9, with a 4.53 ERA, and held batters to a .192 batting average with two outs and runners in scoring position. On September 26, 2008, the Cubs postseason roster was announced, and Marquis was