Modern programs are monolithic, combining code of varied provenance without isolation, all the while running on network-connected devices. A vulnerability in any component may compromise code and data of all other components. Compartmentalization separates programs into fault domains with limited policy-defined permissions, following the Principle of Least Privilege, preventing arbitrary interactions between components. Unfortunately, existing compartmentalization mechanisms target weak attacker models, incur high overheads, or overfit to specific use cases, precluding their general adoption. The need of the hour is a secure, performant, and flexible mechanism on which developers can reliably implement an arsenal of compartmentalized software. We present SecureCells, a novel architecture for intra-address space compartmentalization. SecureCells enforces per-Virtual Memory Area (VMA) permissions for secure and scalable access control, and introduces new userspace instructions for secure and fast compartment switching with hardware-enforced call gates and zero-copy permission transfers. SecureCells enables novel software mechanisms for call stack maintenance and register context isolation. In microbenchmarks, SecureCells switches compartments in only 8 cycles on a 5-stage in-order processor, reducing cost by an order of magnitude compared to state-of-the-art. Consequently, SecureCells helps secure high-performance software such as an in-memory key-value store with negligible overhead of less than 3%.