The Macintosh IIsi was a compact 3-box desktop unit, effectively a cut-down Macintosh IIci in a smaller case, made cheaper by the redesign of the motherboard and the deletion of all but one of the expansion card slots (a single Processor Direct Slot). It was introduced as a low-cost alternative to the professional desktop models for home use, but offered more features and performance than the LC series. It had colour and could drive a number of different external monitors, with a maximum screen resolution of 640 x 480 in 8-bit colour.

It shipped with either a 40 or 80MB internal hard disk, and a 1.44 MB floppy disk drive. The MC 68882 FPU was an optional extra, mounted on a special plug-in card. Ports included SCSI, two serial ports, an ADB port, a floppy drive port, and a microphone/sound input socket.

To cut costs, the IIsi's video shared the main system memory, which also had the effect of slowing down video considerably, especially as the IIsi had 1MB of slow RAM soldered to the motherboard. David Pogue's book Macworld Macintosh Secrets observed that one could speed up video considerably if one set the disk cache size large enough to force the computer to draw video RAM from faster RAM installed in the SIMM banks.

The IIsi also suffered from sound difficulties --- over time, the speaker contacts would begin to fail, and sound would periodically drop out.