Coldcard is a Bitcoin-only wallet aimed at advanced users who want paranoid-grade security. Ledger is a general-purpose wallet for people who hold Bitcoin, Ethereum, Solana and many other assets.
Coldcard offers features like a dedicated secure element, optional air-gapped operation and PSBT signing, which serious Bitcoin holders love. Ledger's security is excellent too, but it is designed for broad usability rather than Bitcoin-specific depth.
This is the biggest practical difference. Coldcard is Bitcoin only, while Ledger supports more than 5,500 assets. If you hold anything besides Bitcoin, Ledger is the only realistic choice of the two.
Ledger is far more beginner-friendly. Coldcard assumes a higher level of technical comfort and rewards users who read the manual carefully.
Coldcard is the enthusiast's Bitcoin vault. Ledger is the everyday wallet for a diversified portfolio. Most people are better served by Ledger.