Yu-Gi-Oh!: Duel Monsters is about an ancient Egyptian pharaoh whose soul is imprisoned within the sennen puzzle (millennium puzzle). His goal is to regain his memories and cross over to the afterlife with the help of a boy named Yuugi Mutou. Together, he and the pharaoh, along with their other friends, battle their enemies through a card game called Duel Monsters where the stakes are high. Add to that the use of the sennen items (millennium items) that have mysterious powers, often weilded by the major villains, open up the Game of Darkness, and depending on the agreed conditions, can result in the loss or death of the other player.
This series focuses more on the card game aspect of Yu-Gi-Oh!. Note that the combination of the first syllables of the main characters' Yuugi and Jounouchi, forms the word yuujou, which in Japanese means friendship. This of course is the theme of Yu-Gi-Oh!, most notable perhaps, with that of Seto Kaiba, who's probably the pharaoh's biggest rival, as well as his greatest ally.
Notes on the 4kids and versions based on it:
The episode count has remained the same, but the episodes have been heavily edited. For an in-depth comparison between the US and Japanese versions see: yu-jyo.net
4kids divided it into a number of seasons:
Season 1: Duelist Kingdom (episodes 1-49)
Season 2: Battle City Duels (episodes 50-97)
Season 3: Enter the Shadow Realm (episodes 98-144)
Season 4: Waking the Dragons (episodes 145-184)
Season 5: Grand Championship (episodes 185-198)
' -Dawn of the Duel (episodes 199-224)