The noble family von Sax or Saxe (originally in Italian de Sacco) was a medieval noble family in eastern Switzerland. They owned estates and castles on both sides of the Alps in the modern cantons of St. Gallen, Graubünden and Ticino. The origin of the family is unknown, but they probably stem from Churrätien nobility and were related to the da Torre family. The family divided into two main lines; the Grafen (counts) von Sax-Misox and the Freiherren (barons) von Hohensax.

The earliest mention of a member of the family is in 1137/39 with Eberhard de Sacco. In 1168, they were granted a fief over the Misox valley, probably as a reward for their support of the Hohenstaufen family. The founder of the line was Albrecht of Sax who first appears in a record in 1188. His brother, Heinrich reorganized the administration of the Abbey of St. Gall and brought it under their authority. Albrecht's sons, Ulrich (first mentioned 1204, died 23 September 1220) and Heinrich (born around 1180, last mentioned 31 March 1247) became the abbot and vogt, respectively, over the Abbey of St. Gall. Between 1208 and 1213 they became vogts over Disentis and Pfäfers Abbeys. In 1212 they supported Frederick II in his bid to become Emperor and gained extensive land and wealth from him. To protect their expansive holdings, the family built Clanx Castle in Appenzell, Hohensax Castle in Sennwald and Mesocco Castle in Mesocco in Graubünden. In 1220, they expanded their southern holdings into the Leventina and Blenio Valleys. The next 28 years marked a high point in the family's power. In 1248, the family holdings were divided between two of Heinrich's grandsons. The southern holdings in Graubünden and Ticino as well as Clanx Castle and Pfäfers Abbey were inherited by Heinrich (first mention 1235, last mention 1258) and Albrecht (first mention 1236, last mention 1275), who became the heads of the Sax-Misox line. The northern estates around Hohensax and St. Gallen were inherited by Ulrich (first mention 1236, last mention 1257) who founded the Hohensax line.

In 1257 Albrecht of Sax-Misox sold Wartenstein Castle and the villages of Pfäfers, Valens, Vättis and Untervaz to Pfäfers Abbey for 300 silver marks. After the decline of the imperial Hohenstaufen family the Sax-Misox lost the Blenio Valley, Monte Dongo and Clanx Castle. Their lands were reduced to the Core of the Misox Valley with the San Bernardino Pass and the Walser settlements in the Rheinwald Valley. The distant estate at Arth was granted as a fief to Heinrich and Albrecht von Grünenfels in 1295.

Caspar of Sax-Misox (1362–90) married Elizabeth of Rhäzüns and after her grandfather died in 1380, inherited the land of the Barons of Belmont including Flims with the Belmont Castle, Graubünden, Fidaz, Gruob, Ilanz, Lugnez, Vals and Wartau. Wartau village was later sold to the Count of Werdenberg.

Caspar and Elizabeth's son, Johann von Sax-Misox (1390–1427) was initially in service to the Visconti family who were the Dukes of Milan. However, in 1402 he and his brother Albert (1390–1406) acquired the Milanese city of Bellinzona. They built castles in Gorduno, Bogiano and Roveredo to protect their conquests. A few years later, in 1406–7, they were forced to accept co-ownership of Bellinzona with Uri and Obwalden. In 1406 Albert of Sax was murdered by a distant cousin at the Torre Fiorenzana near Grono, possibly to gain favor with the Dukes of Milan. In 1413 Johann and another brother, Donat (mentioned 1400–23), supported Emperor Sigismund during his campaigns against the Venetians in Italy and were rewarded with the title of count and the right to mint coins. In 1419 they sold Bellinzona to Uri and Obwalden. When the Confederates attacked Milan in 1425, Johann remained neutral.

On 14 February 1395, the three main nobles (the abbot of Disentis, Johannes von Ilanz, Baron Ulrich II von Rhäzüns and Baron Albrecht von Sax-Misox) of the Vorderrhein together with delegates from the Court Municipalities in Ilanz created an "eternal alliance". Since the alliance was predominantly located in the high country, it was also known as Part Sura (German: Ober Bund or High Alliance). Five days later, Count Johann von Werdenberg-Sargans joined the League at Flimserwald. On 16 March 1424, the leaders, including Johann of Sax-Misox, of the alliance met under a legendary maple tree in Trun to reaffirm and expand it into the Grey League.

Johann married Catherine of Werdenberg-Heiligenberg, the co-heiress with the last Count of Toggenburg, Frederick VII. After Frederick's death in 1436, the Sax-Misox family was one of the claimants to the Toggenburg lands, which led to the Old Zürich War in 1440.

Johann's son Count Heinrich of Sax-Misox (around 1418–last mention 1479) fought to receive the Toggenburg inheritance of his mother Catherine. However, in 1437 one of the castles he claimed, Grinau Castle was given to Schwyz and in 1439 he mortgaged his claim on the county of Uznach to Schwyz and Glarus. He was part of the Confederate army which attacked the Golden Ambrosian Republic in Milan and was decisively defeated at the Battle of Castione on 6 July 1449. By the following year, he was reconciled again with the Duke of Milan. In 1458, when he was preparing to conclude an alliance with Milan, there was an uprising in the Grey League, which was settled amicably thanks to the mediation of the abbot of Disentis. In 1479 he was party to a peace treaty signed by the Swiss Confederation and the Duchy of Milan. In the same year he abdicated and gave his lands to his son Johann-Peter.