[3] Karam won back-to-back oval races at the Milwaukee Mile and Iowa Speedway and finished fifth in points, winning rookie of the year honors.

[4] Karam won the Indy Lights title that year, becoming the eighth rookie to win the series championship.

They returned to the race several laps down, only for Pruett to suffer similar consequences when knocked into the wall by a sports prototype.

[10] With Rojas sidelined due to nagging back injuries,[11] Karam started for his final appearance of the season at the Brickyard Grand Prix, teamed with Pruett in the 01 car.

He competed at the 2017 IMSA WeatherTech SportsCar Championship for the factory-supported team, where his best class finish was fifth at Mosport Park.

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, in Detroit, during a heavy downpour, Karam was on pole with 90 seconds left in qualifying when IndyCar canceled the session due to track conditions.

In his homecoming at Pocono Raceway in Long Pond, Pennsylvania for the 2015 ABC Supply 500 on August 23, Karam was leading with 21 laps remaining when he lost control exiting turn 1, eliminating his Chip Ganassi number 8 Dallara as it spun and crashed hard into the wall.

Debris strewn from Karam's disintegrating car made contact with fellow competitor Justin Wilson's helmet, sending him into the infield wall where the safety team extracted him unconscious and unresponsive, necessitating an emergency medevac to Lehigh Valley Hospital–Cedar Crest in Allentown where Wilson lay comatose, in critical condition.

Replaced for the 2016 season, Karam's seat in the Chip Ganassi stable piloting the number 8 Dallara was secured by Max Chilton.

On a one-race agreement for 2016, Dreyer & Reinbold signed Karam for the Indianapolis 500, initially with Havoline and Gas Monkey Garage as sponsors.

Steadily improving from his 23rd qualifying slot on grid, into the top 10, Karam crashed on lap 94, going into Townsend Bell in Turn One.

Having improved from his 21st qualifying slot into the top 10, Karam retired his Mecum Auctions Dreyer & Reinbold entry at the 275-mile juncture, with a dead battery.

[22] On May 23, 2021, Karam joined Will Power of Australia and Simona de Silvestro of Switzerland as the final three drivers to qualify in the 11th and last row for the 105th running of the Indy 500.

31 for Jordan Anderson Racing in the Xfinity Series' Pennzoil 150 at the Indianapolis Motor Speedway road course.

[29] On September 14, 2022, Karam stated in an interview with Dustin Albino from Jayski that he would like to have a full-time NASCAR ride in 2023 after having run part-time in 2021 and 2022.

[30] On December 2, it was announced that Karam would return to APR to run at least 17 races for them in 2023 with the possibility of a full season if sponsorship can be found.

[35] Karam did not end up getting a full-time NASCAR ride again in 2024 and on January 23 was announced to run part-time for Sam Hunt Racing again in the Xfinity Series beginning at the season-opener at Daytona in the team's No.