Mixolydian mode may refer to one of three things: the name applied to one of the ancient Greek harmoniai or tonoi, based on a particular octave species or scale; one of the medieval church modes; or a modern musical mode or diatonic scale, related to the medieval mode. (The Hypomixolydian mode of medieval music, by contrast, has no modern counterpart.)

The modern diatonic mode is the scale forming the basis of both the rising and falling forms of Harikambhoji in Carnatic music, the classical music form of southern India, or Khamaj in Hindustani music, the classical music form of northern India.

The idea of a Mixolydian mode comes from the music theory of ancient Greece. The invention of the ancient Greek Mixolydian mode was attributed to Sappho, the 7th-century-B.C. poet and musician. However, what the ancient Greeks thought of as Mixolydian is very different from the modern interpretation of the mode. The prefix mixo- (μιξο-) means "mixed", referring to its resemblance to the Lydian mode.

In Greek theory, the Mixolydian tonos (the term "mode" is a later Latin term) employs a scale (or "octave species") corresponding to the Greek Hypolydian mode inverted. In its diatonic genus, this is a scale descending from paramese to hypate hypaton: in the diatonic genus, a whole tone (paramese to mese) followed by two conjunct inverted Lydian tetrachords (each being two whole tones followed by a semitone descending). This diatonic genus of the scale is roughly the equivalent of playing all the white notes of a piano from B to B, which is also known as modern Locrian mode.

In the chromatic and enharmonic genera, each tetrachord consists of a minor third plus two semitones, and a major third plus two quarter tones, respectively.

The term Mixolydian was originally used to designate one of the traditional harmoniai of Greek theory. It was appropriated later (along with six other names) by 2nd-century theorist Ptolemy to designate his seven tonoi or transposition keys. Four centuries later, Boethius interpreted Ptolemy in Latin, still with the meaning of transposition keys, not scales.

When chant theory was first being formulated in the 9th century, these seven names plus an eighth, Hypermixolydian (later changed to Hypomixolydian), were again re-appropriated in the anonymous treatise Alia Musica. A commentary on that treatise, called the Nova expositio, first gave it a new sense as one of a set of eight diatonic species of the octave, or scales. The name Mixolydian came to be applied to one of the eight modes of medieval church music: the seventh mode. This mode does not run from B to B on white notes, as the Greek mode, but was defined in two ways: as the diatonic octave species from G up one octave to the G above, or as a mode whose final was G and whose ambitus runs from the F below the final to the G above, with possible extensions "by licence" up to A above and even down to E below, and in which the note D (the tenor of the corresponding seventh psalm tone) had an important melodic function. This medieval theoretical construction led to the modern use of the term for the natural scale from G to G.

The seventh mode of western church music is an authentic mode based on and encompassing the natural scale from G to G, with the perfect fifth (the D in a G to G scale) as the dominant, reciting note or tenor.