During the 2015 IndyCar Series season Karam split the driving duties for the Chip Ganassi Racing No. 8 Dallara with Sebastián Saavedra, who ran four races on a limited budget. While his season started slowly, by finishing in the lower third of the field in his first three road/street courses events of the season, he proved to be a quick study on the ovals. At Indianapolis, he was at the top of the speed charts on the opening day of practice and consistently remained among the top cars in successive sessions. After qualifying 23rd, with a conservative setup, he was on top of the speed charts again during the post-qualifying practice and 7th quickest during Carb Day. Considered to be a dark-horse favorite on race day, it was all for naught as he was forced to settle with a 32nd-place finish in the 2015 Indianapolis 500, after contact with Takuma Sato. At the next race, which was at Detroit, in a heavy downpour, Karam was on pole with 90 seconds left in qualifying when IndyCar canceled the session due to track conditions. Following his 3rd place qualifying effort and leading 5 laps on his way to a 5th place finish at Fontana, Karam captured his season best finish at the 2015 Iowa Corn 300 at Iowa Speedway in July, by finishing 3rd.