Uncle Scrooge's nemesis Flintheart Glomgold is portrayed in this series as a Scot. In the original comics, he was portrayed as South African; this was removed due to the apartheid regime that was part of that country's history.
In the comics Donald Duck was not in the navy, and always accompanied Uncle Scrooge, Huey, Dewy, and Louie in the their adventures. However, the show's creators thought that he might steal the focus from Scrooge and that his voice would be to hard to understand. Launchpad McQuack was instead used as a substitute for Donald.
In Carl Barks comics, the Beagle Boys have no individual personalities and they all look the same, they are only mentioned by their numbers and they all begin with "176". On the show, the Beagle Boys were given names and different personalities.
The series was the first Disney cartoon to be produced for syndication. The studio gambled on the idea that a larger investment into quality animation could be made back through syndication - a concept that worked well with live-action TV reruns, but which had only been used with inexpensive cartoon series that either recycled theatrical shorts from decades past or only featured limited, low-budget animation. However, this show was a big hit and paved the way for future Disney cartoon series, such as Chip 'n' Dale Rescue Rangers (1989), TaleSpin (1990), and Gargoyles (1994).
In the Carl Barks comics, Scrooge McDuck was much greedier and meaner, who could be portrayed as much an antagonist as a protagonist. He was considerably toned down in this series to be more affectionate and kindhearted.
Disney invested a far greater amount of money into the TV series than had previously been spent on animated shows of the time. This was considered a risky move, because animated TV series were generally considered low-budget investments for most of the history of TV cartoons up through the 1980s.