He is voiced by Tony Anselmo as an adult, Don Cheadle, (who also portrayed War Machine) when speaking in Barksian Modulator, and the late Russi Taylor (who also voices Minnie Mouse, and Huey, Dewey, and Louie & Webby Vanderquack from original DuckTales) as young.
Like in the comics, Donald's main character traits are his bad luck and short temper, but his loyalty and perseverance shine when he gives his all for the ones he loves.
- Scrooge McDuck is Donald's uncle through his youngest sister, Hortense McDuck. He used to live with Scrooge inside McDuck Manor at least by his pre-teens, where they spent a lot of time together when he was younger, going on many adventures with Scrooge and his sister Della. After Della's disappearance into space on a rocket Scrooge built, Donald and Scrooge had a falling out due to Donald blaming Scrooge for the disappearance of Della, even though Scrooge spent half of his fortune attempting to bring her back. This lasted for ten years until the beginning of the series, when Donald asked Scrooge to babysit his nephews, due to almost being late for a job interview. Donald was skeptical and nervous to leave his nephews with Scrooge at first and later had his fears confirmed when he learned of Scrooge including the boys on his expedition to Atlantis. However, he eventually realised that Scrooge could also teach the boys how to survive tough situations, while admitting he was overprotective. Due to an explosion on Donald's boat caused by Dewey for keeping the engine running, Scrooge agreed to letting them move into McDuck Manor. At times, Donald and Scrooge have shown to still care for one another deep down, as seen in "The Most Dangerous Game...Night!" when Donald and Scrooge share a brief hug over winning, but try to shrug it off as nothing with a handshake soon after. Scrooge then admits he considers Donald a moocher that lives in his pool and eats his food, even though he's assisted him on a few profitable adventures. He and Scrooge mostly have a love-hate relationship, for example in "The Town Where Everyone Was Nice!" when he consistently hesitated to give Donald money to impress his friends, but also refused to lose Donald after learning he wanted to bring the band back together. Also in "The 87 Cent Solution!" when the fake funeral was being held for Scrooge, Donald was the only one who wasn't told about the setup, leading him to believe he actually was dead. He can be seen mourning in front of the casket and even fainting at the sight of Scrooge still being alive, showing how much he truly still cares about his uncle's well-being.
- Della is Donald's twin sister who isn't currently around, he does her the favour of being her children's guardian. Not much is said about Donald and Della's relationship, but based on Donald'Donald's behaviour in "The Spear of Selene!", it's shown that Donald is very sensitive about her disappearance. In Last Christmas! Donald was going through a punk rock phase, and try to become mature and independent in the process, but, he ends up leaving Della behind upsetting her. Yet he sees that later and is genuinely sorry about it that he apologise for and promises to stick together from then on. Before the events of "Woo-oo!", Donald and Della were very close, as they traveled the world and went on adventures with their uncle Scrooge. Their relationship however had ended on a sour note for more than 10 years, as explained in "The Last Crash of the Sunchaser!", when Donald was seen yelling at Della in a flashback about the risks of the outer space expedition she was intending on achieving. It is unknown whether or not they had another conversation before Della stole the Spear of Selene.
- Huey, Dewey, and Louie are Donald's nephews and as well as being their uncle, Donald is also their guardian. Even though they can troublesome Donald loves them unconditionally as if they were his own kids, and ten years with them has brought him to the point where Donald has become an overprotective father-figure to the triplets. In the events of ``Woo-oo!`` his protectiveness had gone to a ridiculous extent, and as seen in photographs Donald helps Dewey take his first steps while being surrounded by pillows, and when Donald is shown to have Huey wear football fatigues just to be the water boy. Yet even if he goes overboard his parental nature is in the right place. As shown time and time again that he will risk his own life to rescue his nephews.
- Donald and Gladstone are cousins, and as they grew up they spent a lot of time together. However, even though he's family, Donald always had a strong dislike and even envy of Gladstone's luck. During their time growing up together, whenever something good happened to Gladstone, something bad happened to Donald; this irritated Donald making him feel insignificant. Yet despite their stark difference in fortune, he would still help him out because Donald is always there for family. This is shown in "The House of the Lucky Gander!".
- Donald Duck knew Mrs. Beakley when he was younger during his "better" time with his Uncle Scrooge. At the end of "Woo-oo!" when Beakley talked to her granddaughter Webby, and allowed her to continue to go on adventures with Scrooge, her influence lead to Donald giving his nephews more freedom and permission to continue to go on adventures with Scrooge. However, in "Daytrip of Doom!" Donald and Beakley got into a fight over house rules, with Beakley getting into an argument with Donald about breaking fire laws, and using up the water bill. This, in turn caused Donald to order multiple generators for his boat, with Beakley making the remark "He is going to kill himself." They finally worked together when Donald showed her the ransom note left by the Beagle Boys. When they go up against the Beagle Boys, Beakley was impressed how tough Donald was and by the end of the episode, Donald and Beakley were talking and appeared to be getting along better than before.
- Very little interactions are shown between Donald and Webby, but Webby is known to be a fan of Donald and similar to Scrooge, idolises him as one of the greatest adventurers of all time. As seen in "The House of the Lucky Gander!", when he won, she hugged him. Then, in ``The Shadow War!`` when Donald said "Get away from my kids" as he was fighting off Magica's shadow army, there may be implication that Donald has accepted her as his honorary niece (although he has not given her permissiom to call him Uncle Donald yet, like Scrooge did). Like his nephews, he also wants to protect Webby, for example in "The Town Where Everyone Was Nice!", when she was tied up by a plant tentacle he rescued Webby along with his nephews. And in "The Golden Spear!", in the nearly end she gave him goodbye hug when they send him to the vacation.
- Panchito Pistoles and José Carioca are Donald's best friends from college, with who he made a band with, named The Three Caballeros.