Likely Anna and Vytautas were married around 1370. Anna first comes to light in 1382 when her husband was imprisoned in the Kreva Castle by his cousin Jogaila during the Lithuanian Civil War (1381–1384). While all accounts agree that she freed her husband, details vary from source to source. It is unclear how much freedom Anna had in Kreva and if she was guarded. It is written in the Lithuanian Chronicles that she had two maids with her. She convinced one of them to exchange clothes with Vytautas who then escaped undetected. Wigand of Marburg claimed that Vytautas dressed in Anna's clothes rather than one of Anna's maids. It is believed that Anna remained in Kreva and no information is available on how she escaped or was released. Teodor Narbutt (1784–1864) later added many colorful details to the story, including Vytautas illness and maid Alena, who sacrificed herself to save her master.
In 1389, when her husband's coup to capture Vilnius failed, she was in Hrodna. After the failed coup Anna followed her husband to the Teutonic Knights, where Vytautas asked for an alliance against his cousins Jogaila and Skirgaila in the Lithuanian Civil War (1389–1392). For a while she was held hostage to guarantee that Vytautas would not break the alliance. After the disagreements were settled in 1392, Anna confirmed the Ostrów Agreement, the peace treaty which made Vytautas the Grand Duke of Lithuania. She signed two letters, one given to Jogaila and another to his wife Jadwiga of Poland. Anna continued to be active in political life and attended negotiations for the Treaty of Salynas (1398).
Before 1396, she and her husband traveled to Késmárk to meet King Sigismund of Hungary to establish a friendly relationship. While they spoke for a long time, half of the city burned, leading the Hungarian nobles to think that Vytautas's people had to do with it. Sigismund intervened and cleared up the situation, resuming the negotiations. After the visit was finished, the Duke and his wife Anna gave many presents to Sigismund including a coat, a hat and gloves made of sable-skin and embroiled with gold. The details of all these presents "given by Vytautas's wife" remained in a chronicle from the end of the 15th century written by Eberhard Windercke, close servant nobleman of the Hungarian King (who later was also King of Bohemia and Holy Roman Emperor).
In 1400, Anna visited the tomb of Dorothy of Montau in Marienwerder (modern Kwidzyn), and prayed in the churches of Saint Anne in Brandenburg and of Saint Barbara in Oldenburg. She was accompanied by her brother-in-law Sigismund Kęstutaitis and an escort of 400 men. Anna was greeted with expensive gifts and lavish receptions. Anna continued to maintain good relationship with the Teutonic Knights, who sent her expensive gifts, including clavichord and portative organ in 1408 and rare wine in 1416. After her death all churches in Prussia were ordered to hold requiem masses. Various chronicles and documents recorded much less positive interaction between Anna and Poland.
It is believed that St. Anne's Church, built in Vilnius Lower Castle before 1390, was so named in Anna's honor. It was later known as St. Barbara's Church but did not survive to the present. Flemish traveler Guillebert de Lannoy wrote favorably about the Grand Duchess.
After her death in 1418 Vytautas wanted to marry her niece Juliana Olshanski, daughter of Ivan Olshanski. Polish historian Jan Długosz asserts that Ivan of Karachev, first husband of Juliana, was murdered by Vytautas in order to marry her. The Bishop of Vilnius refused the ceremony due to their close relationship (Vytautas was Juliana's uncle-in-law) and demanded they seek approval from the pope. Eventually the Bishop of Włocławek performed the ceremony.
There is considerable debate about who the parents of Anna were. According to the Bychowiec Chronicle, a late and unreliable source, Anna was a sister of Yuri Svyatoslavich, the last sovereign ruler of Smolensk. For a long time this was the only theory about her origins.
In 1933 Lithuanian historian, Ignas Jonynas, published a study in which he attempted to debunk the Bychowiec Chronicle and demonstrate that Anna was not an Orthodox duchess from Slavic lands, but a daughter of local Lithuanian noble. Jonynas pointed out that no other contemporary sources mention the relationship between Vytautas and Yuri even though Lithuania and Smolensk were at war several times. The First Lithuanian Chronicle, the basis for which was written while Vytautas was still alive, describes in detail how wars against Smolensk was waged in 1386, 1395, 1401, and 1404, but mentions nothing about Vytautas and Yuri being in-laws. He argued that Anna was a sister of Sudimantas, a nobleman from Eišiškės and commander of Vytautas' army. Teutonic Chronicle mentions Sudimantas as swoger of Vytautas. At the time swoger meant brother-in-law. Another document from 1416 refers to Sudimantas as magen, which denoted a relative, usually related by blood. Since Jonynas' study Sudimantas has been variously presented as Anna's brother, father, or sister's husband.
Polish historian Jan Tęgowski disagreed with Jonynas and argued that both Sudimantas and Lev of Drutsk (who is also mentioned as Vytautas' swoger) were married to sisters of Vytautas's first wife, Princess Maria of Lukoml. Jonynas expressed serious doubts if Maria, daughter of Andrei, existed at all. Information about her is found in the same unreliable Bychowiec Chronicle. The only contemporary source that mentions Maria of Lukoml dates from 1440–1443 and concerns division of her estate after her death and makes no mention of her relationship to Vytautas. Tęgowski also pointed out that a document from 1413 mentions a "Russian duke Basil" as Vytautas's brother-in-law. Indeed, one of Yuri's (and, by extension, Anna's) brothers was named Basil.