Paul Morigi/Getty Images for Fortune/Time Inc Greta Van Susteren.
Brit Hume will take over as the new host of "On the Record."
"We are grateful for Greta's many contributions over the years and wish her continued success," Fox News co-presidents Jack Abernethy and Bill Shine said in a statement.
Abernethy and Shine added: "As one of the best political analysts in the industry, Brit is the ideal choice to host a nightly political program while the most dynamic and captivating election in recent history unfolds. Having Brit at the helm of this show will enable Fox News to continue on track to have its highest-rated year ever as the network dominates the cable news landscape."
Hume previously anchored "Special Report," the network's flagship weekly political news show. He retired as the show's host in 2008 and transitioned to senior political analyst.
Hume said in a statement that he was "happy to take on" his new assignment during this "extraordinary election."
"My Fox News colleagues have set a high standard for political coverage which I'll do my best to uphold," he said. "I'm honored to be asked."
Van Susteren, who gained notoriety during the O.J. Simpson murder trial as a legal analyst on CNN, had been with Fox News since 2002 and was a staple on the network.
It was not immediately clear why Van Susteren was leaving the network. The news came the same day 21st Century Fox announced it had settled former host Gretchen Carlson's sexual harassment lawsuit against ex-CEO Roger Ailes. Several Fox News hosts had so-called key-man clauses allowing them to exit if Ailes were to depart.