Originally designed around the 16-bit 286 microprocessor and called the AT bus, the ISA bus has 24 address and 16 data lines, sufficient to handle 16 megabyte memory I/O addresses. The ISA bus is limited to a slow 8 MHz clock speed and for this reason, faster peripherals and memory left the ISA bus behind soon after its development. Unlike the earlier 8-bit PC/XT bus, the ISA bus includes two connectors. In addition to the single, 62-pin, 8-bit PC/XT bus connector, the ISA bus includes a second connector with four additional address and eight additional data lines, interrupt, and DMA control lines. Although IBM documented every pin on the ISA bus, they never published strict timing specifications to signals on the bus. As a result, ISA bus system developers designing products for many platforms had to guess at timing.

Problems developed as a result of holding the ISA bus to 8 MHz for backward compatibility. Some anxious manufacturers pushed the system speed causing products with marginal operations characteristics, especially when extra memory was added to high-speed PCs. Since the IEEE ISA standard of 1987, the bus signals have remained unchanged. In 1993, Intel and Microsoft announced a joint development, Plug and Play ISA, a method for making expansion boards work with the ISA bus, eliminating the need for DIP switch settings, jumpers, interrupts, DMA channels, ports, and ROM ranges. The Plug and Play card tells the host computer what resources it requires. This requires a large software-based isolation protocol which keeps an expansion board switched off until it can be addressed, allowing one card to be polled at a time because slot-specific-address enable signals for expansion cards are not part of the ISA specification. In 1987, the ISA bus made way for the IBM PS/2 “clone-killer” computer “Micro Channel” bus however, the clone makers initially ignored the PS/2 and Micro Channel.