Like Elvis says, there are a few places to start, depending on what you want:
The Colour of Magic is the first Discworld book - it is funny, but in a much less subtle way than later books. Rincewind, the main character, also appears in **The Light Fantastic, Eric, Sourcery, Interesting Times, The Fifth Continent and The Last Hero.
Guards! Guards! is the start of the watch series (followed by Men-At-Arms, Feet of Clay, The Fifth Elephant and Night Watch. This is a very good series, filled with very subtle humour (as well as a bit of slapstick thrown in).
Equal Rites sort of starts off the witches series, but only stars one of the witches. The three witches first appear together in Wyrd Sisters followed by Witches Abroad, Lords and Ladies and Carpe Jugulum
Mort is the first book of the DEATH series, followed by Reaper Man, Soul Music and Hogfather
In short, if you like slapstick humour, go for Rincewind. If you like what we could loosely call ‘political satire’ or ‘film noir-spoof’ humour, go for City Watch. If you like rural humour or psychological (or headological) humour, try witches. The Death series often has a lot of ‘real-world’ tie-ins, although this is common in many TP books.
Apart from these, there are also a number of ‘stand-alone’ books, which feature characters that only appear in that book. Any of these would be good if you want to just read one book to get an idea of Pterry’s style. (Although none of the ‘series’ books actaully requires you to have read one of the others)These are:
** pyramids** - quite a good story but not one of my favourites
Small Gods - Good if you like religious humour
The Truth - My favourite of the standalones, highly recommended
I think that covers all of them. Whichever one you pick, go and read the Annotated Pratchett File when you’ve finished, and realise how many jokes you missed…