The Fender Duo-Sonic guitar was introduced by Fender in 1956 as a “student” model guitar. Like the Musicmaster introduced a few months earlier, it featured crude but effective construction and a 22.5 inch scale length (standard Fender guitars feature a 25.5 inch scale). The “Duo-Sonic” features two pick-ups and a vertical (as opposed to Fender's standard blade-style) selector switch on the lower horn of the body.

In 1964 both models were redesigned based on the Fender Mustang that had recently been added to the student model line. All three guitars now featured larger and slightly offset bodies, necks with larger headstocks and rosewood fingerboards and plastic pickguards with the volume and tone controls mounted on a separate metal plate. Pick-up selection was moved above the pick-ups on both the Duo-Sonic and the Mustang and utilized two 3-position on-off-on switches that allowed for in and out-of-phase sounds. The pickups were also reverse-wound/reverse-polarity, which made them into a functional Humbucker when both pick-ups were used simultaneously. Also added in this redesign was the option of a 24 inch scale neck in addition to the 22.5 inch scale. This re-designed model was re-named Duo-Sonic II although decals with and without the II designation were used occasionally.

The Duo-Sonic lasted until 1969 when it was dropped most likely because the Mustang with its tremolo tail piece was far more popular. It was reissued in the middle of the 1990's, yet was again discontinued in 1997.

The Duo-Sonic is closely identified with Liz Phair though it was used by David Byrne of the Talking Heads early in their career as well as Jimi Hendrix (when he toured the under the name Jimmy James with The Isley Brothers). Johnny Winter also used a modified Duo-Sonic during the late 1960s and early 1970s, particularly on his first few albums. Patti Smith also plays a Duo-Sonic and has featured her guitar in song lyrics, for example in "Radio Ethiopia/Abyssinia" from the Radio Ethiopia LP. Tom Cummings from Human Condition uses the late 90's remake Duo-Sonic.

The Duo-Sonic I and II are both considered rare and have displayed growing collector value. The Duo-Sonic II in particular is often seen as a desirable alternative to the more popular Mustang, since it negates the difficult-to-maintain tremolo bridge.