At the heart of the story is the deep friendship between Wilbur and Charlotte. Wilbur, insecure and facing a bleak future, finds solace and courage in Charlotte's unwavering belief in him. Charlotte, despite their differences, embraces Wilbur unconditionally and dedicates herself to his well-being. Their friendship highlights the importance of companionship, loyalty, and the lengths we go to for those we care about.

The story delicately addresses the cycle of life and death, particularly relevant in a farm setting. Wilbur's initial naiveté about his fate is contrasted with Charlotte's acceptance of her own mortality. She prepares Wilbur for the future, teaching him about the beauty and inevitability of life's transitions. The cycle is further emphasized by the arrival of Charlotte's children, signifying continuity and hope even in the face of loss.

E.B. White weaves a powerful message about extending kindness and understanding to all creatures, big and small. Fern, the young girl, shows immense compassion in saving Wilbur's life. Charlotte, often perceived as scary or undesirable, is revealed to be a complex and caring individual. This theme encourages young readers to look beyond appearances and recognize the value in all living things.