To define a model in Django, start by importing models from django.db. Then create a class that inherits from models.Model. Inside this class, add fields as attributes using Django's field types, such as CharField for text and IntegerField for numbers. Each field can have options like max_length to limit text size. After saving your model, run 'python manage.py makemigrations' to create migration files that describe database changes. Then run 'python manage.py migrate' to apply these changes and create the corresponding database table. This process connects your Python model class to a real database table, ready for storing data.