Collect 99 souls, and then 1 witches soul. To do so lets you become a Death Scythe. This gives you the privilege of getting to be one of Lord Death's personal weapons. This is the basis of the first few episodes. Meisters fighting alongside Weapons to collect souls and defeat witches.
Lord Death decided to start a school in which to train young Meisers and Weapons to become successful reapers themselves. These Weapons are also students as they are beings that can turn into weapons(capable of evolution). The weapons vary on what they become, such as twin guns, blades, scythe, gloves, a spear, a lantern, and more. The meisters must connect their own souls to their weapons so that they resonate at the frequency. By doing so they are able to unlock their full potential.
The show mostly follows 3 meisters and their weapons. Maka and her scythe Soul. Blackstar and his blade Tsubaki. Death the Kid and his twin guns Liz and Patti. Each has their own backstory and life issues that are manifested throughout the series. These 7 join forces repeatedly, but also fight each other just as often.
The students are sent on a few "simple" missions that turn out to be not as simple. Eventually these missions add up to the great Arachnophobia, a witch from long ago returning to the world. She then releases the Kishin, Asura. A being that started as a Meister who then ate the soul of his own weapon. Following this there are missions to obtain odd magical objects, then the final showdown.
There of course is plenty more, like the teacher Franken Stein who likes disecting and stitching things back up. Or the witch Medusa who uses a variety of snakes to succeed in her goals. Or even Maka's incredibly creepy father who in the Dubbed version is voiced by Vic Mignogna, though you would most likely know him more as the voice of Edward Elric from Fullmetal Alchemist.
Honestly though, I wasn't that big of a fan. Maybe it was because I kept comparing it to other animes like Fullmetal Alchemist, or Dragonball Z and more. But the story was pretty weak, and rather boring at times. The ending was a little more entertaining, but even that ended with a message of heart bullshit. Some of the fights were entertaining, but they had a lot of talk. Then finally there was Lord Death. He was just obnoxious. In the end I can only give the show a 5 out of 11. I wouldn't recommend it.