'As the World Turns', which followed the daily dramas of residents in fictional Oakdale, Illinois, will end in September next year.
The show launched in 1956 and averaged 2.5 million total viewers this year, down from 2.6 million in 2008, according to Nielsen. In comparison, another CBS soap 'The Young and the Restless', averaged just over five million.
Procter & Gamble, which invented the soap opera and gave the genre its name, said it would try and find a new home for the series, .
The consumer products manufacturer has owned more than 20 soap operas in the past 80 years.
CBS also ended 'Guiding Light' earlier this year, which had been on air through radio and TV for 72 years.
Leslie Moonves, the chairman of CBS, said: "Is it the end of an era? It's certainly the end of the client-owned soap.
"All good things come to an end, whether it's after 72 years or 54 years or 10 years. It's a different time and a different business."
Actors including Marisa Tomei, Meg Ryan and James Earl Jones have appeared in 'As the World Turns' at various times. The show also had the longest-running continuing character in television history - Nancy Hughes, played by Helen Wagner, now 91.
Separately, CBS has said its fourth quarter earnings were better than the preceding three quarters, buoyed by higher prices paid for advertising time sold closer to when TV programmes aired.
Speaking at the UBS media conference in New York yesterday, Moonves said that advertisers are now paying 25% more for TV commercial time than they did in the spring.
Moonves also said CBS has sold about 90% of the commercial time available for the Super Bowl on February 7, which is on pace with ad sales the NBC network reported ahead of this year's game.
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