The Nazareth graduate had led the race briefly.
Sage Karam crashed hard during a battle for fifth place at the Indianapolis 500.
Karam was on the outside of Townsend Bell and couldn't hold the line, sending him into the outside wall on the 95th lap. Karam skidded several hundred feet along the barrier but stayed out of traffic.
"Man (I am) super bummed for the Dreyer & Reinbold Racing crew," Karam wrote on Twitter. "(I)Had a car that could win today. Wrong place wrong time."
Karam, who briefly led during pit stops, crashed on the first lap a year ago.
Karam, a Nazareth graduate and son of Liberty wrestling coach Jody Karam, was back at an IndyCar race for the first time since a wreck at Pocono last year during which his car's nosecone bounced into Justin Wilson's cockpit. The impact killed the 37-year-old British driver.
Wilson's younger brother, Stefan Wilson, was also running in this year's Indianapolis 500.
Sage Karam had spent the winter as his father's assistant coach at Liberty.