Khosrowshahi, who led the parent of Expedia.com for 12 years, will remain a board member.
Okerstrom, who had been chief financial officer and executive vice president of operations for the last six years, was also named to the board, said the company, whose other websites include Hotels.com, Hotwire.com, Travelocity.com and Orbitz.com.
"There was no other candidate that the board considered," Expedia Chairman Barry Diller said in a statement.
Okerstrom was Khosrowshahi's "principal partner" in running Expedia, the company said. During Khosrowshahi's tenure, Expedia became the largest online travel agency by bookings and its stock price grew more than six-fold.
On a conference call with reporters on Wednesday, Okerstrom described Uber and Expedia as "complementary" businesses and hinted at a possible future partnership between the industry leaders.
"Given our close relationship, who knows? There's probably ways that we can work much more closely together than we ever have before," Okerstrom said.
"We now have a much closer tie to Uber than we've ever had before. And, yeah, sure, keep your eye out. Maybe there will be something that comes out."
Expedia shares edged up 0.2 percent in extended trading after closing 0.4 percent lower at $143.44 (110.96 pounds).
(Reporting by Alana WIse in New York and Arunima Banerjee in Bengaluru; editing by Anil D'Silva and Richard Chang)
