The show stars the titular Ed (Seán Cullen), a cheerful but none-too-bright dog loved by everyone. Ed's best friend is his polar opposite Doug (Patrick McKenna) an intelligent but unlucky squirrel who everyone calls "Buddy" but nobody likes. Despite their differences, Ed and Doug consider themselves best of friends and have many adventures — and misadventures — in their town of Swellville.
Best Ed contains examples of:
- Amazing Technicolor Wildlife: The Kitten Twins Betsy and Buster are pink, Heiny is a blue Scottish Terrier, and Ed himself is a yellow dog.
- Butt-Monkey: Doug is vehemently despised by everyone in Swellville and extremely unlucky.
- Chronic Hero Syndrome: Ed is obsessed with helping (he even has "I'm here to help!" as one of his catchphrases), but ends up being more of a burden than anything.
- Creepy Twins: Despite seeming cute and innocent on the surface, Betsy and Buster are quite psychotic. They mainly show their true nature around Buddy, whom they greatly despise and enjoy suffering. They also tend to speak in unison.
- Dogs Are Dumb: Ed isn't very smart in contrast to his best friend.
- Gleeful and Grumpy Pairing: The upbeat and sociable Ed is the Gleeful one to the easily irritable but often realistic Buddy's Grumpy.
- In-Series Nickname: Doug is called "Buddy" by everyone in Swellville... although Ed is the only one who considers him a friend.
- Interspecies Romance: Miss Fluffé, a hamster, has a crush on Ed, a dog.
- Keet: Ed is very cheerful and hyperactive, to the point where he tends to mess things up (especially for Buddy).
- Kindhearted Simpleton: Ed, which is part of the reason the people of Swellville all love him.
- Odd Friendship: Ed and Doug are polar opposites in both personality and lot in life, but consider each other best friends.
- The Scapegoat: Buddy often gets blamed for things done by Ed.
- Show Within a Show: Ed is a fan of "The Mighty Measel Moles", which can be described as Star Trek with moles.
- World of Funny Animals: The inhabitants of Swellville are anthropomorphic animals.