The broadcast included Couric's interview with another history-making woman, Secretary of State Hillary Clinton, who became the first former first lady to win elected office when she joined the Senate in 2001.
Couric discussed President Obama's foreign policy speech on developments in the Arab world with Clinton, who also sought the presidency in 2008.
Clinton also addressed negotiations with Israel and the Palestinians, and Washington's policy toward Pakistan in the wake of Osama Bin Laden's death in a U.S. military raid.
The show began with a report on accusations of doping against Tour de France winner Lance Armstrong made by one of his former teammates, Tyler Hamilton.
Other stories reported on an experimental treatment for paralysis victims, the initial public offering for the professional networking site LinkedIn, and the progress of Rep. Gabrielle Giffords, who was gravely wounded earlier this year during a mass shooting in Arizona.
Couric also used her final evening news broadcast, which capped a sometimes troubled run that began in September 2006, to look back on the events and people she had covered since she assumed the anchor chair at CBS.
"It's been an extraordinary privilege to sit in this chair," she said, introducing the segment.
Included were interviews with President Bush, Alex Rodriguez, Clint Eastwood, President Obama, Iranian President Mahmoud Ahmadinejad and perhaps most memorably, Republican vice presidential candidate Sarah Palin, who seemed ill-prepared for many of Couric's questions.
The segment also included clips on her reporting on the war in Iraq, wildfires in California, the attempted bombing in Times Square and last summer's oil spill disaster in the Gulf of Mexico.
Couric ended the broadcast after the montage, thanking viewers "for coming along with me on this incredible journey.
"That's the CBS Evening News for tonight. I'm Katie Couric. Good night," she said.
Couric moved to CBS News after 15 years as co-host of NBC's top-rated morning show, "Today," and at the time spoke of plans to revamp and update the nightly network news format.
She recently said that was overly ambitious, and it might have proven more successful to do a traditional broadcast format and introduce changes only gradually.
During the broadcast's early days, some observers focused on Couric's style and appearance, drawing criticism that male anchors would never have been subject to such surface details.
Couric won a number of prestigious awards during her relatively brief tenure and scored journalistic coups, but never managed to lift "CBS Evening News" out of third place behind "NBC Nightly News" and "ABC World News."
"60 Minutes" reporter Scott Pelley will succeed Couric, whose contract is up in June, on June 6.
Couric, 54, is reported to be in talks to develop a daytime talk show.
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