Alyssa Velaryon was born in 7 AC to Aethan Velaryon and his lady wife, Alarra Massey. Though she had several brothers and cousins in House Velaryon, she was her father's only daughter and thus the apple of his eye. In 22 AC, Alyssa married her cousin, Aenys Targaryen, in a political match, as the king lacked a sister. She gave him six children. Rhaena (23 AC), Aegon (26 AC), Viserys (29 AC), Jaehaerys (34 AC), Alysanne (36 AC), and Vaella Targaryen (39 AC, who died in the cradle)

When Aegon died and her husband Aenys took the throne, Alyssa became queen. It was said that the birth of her sixth child is what drove her brother in law Maegor to take another wife (after having refused Dowager Queen Visenya's offer to marry their eldest daughter Rhaena to her son, Maegor). After fleeing to Dragonstone following the rebellious actions of the Warrior's Sons and the Poor Fellows, her husband Aenys died. While she sang a dirge at his funeral, she did not stay long, spiriting her three youngest children away to her father's seat of Driftmark and proclaiming her eldest son Aegon king. 

However Aegon was never meant to take the throne. Having been jeered by the smallfolk and lords alike for his incestous marriage to his sister Rhaena, he found himself abandoned when Dowager Queen Visenya brought her son Maegor back from exile in Essos, proclaiming him king over the young prince. Alyssa was convinced to bring her children to the court for the marriage of Maegor to Tyanna of the Tower. Her presence at court started rumors that she had abanonded her son's cause, however Queen Tyanna warned Maegor that she had secretly been communicating with Storm's End, the Eyrie, Winterfell, and Casterly Rock, all in an attempt to get them to side for Aegon.

Despite all her efforts, Aegon died in the Battle of the Gods Eye and Alyssa became a prisoner in all but name to Dowager Queen Visenya, along with her two youngest children, Alysanne and Jaehaerys. Her oldest surviving son was sent to court as King Maegor's cup bearer, a fancy title for a hostage. When Visenya died in 44 AC, Alyssa took the opportunity to escape Dragonstone with her children, stealing the Valyrian steel blade Dark Sister. This lead to the death of her eldest son Viserys, who was tortured for nine days until his death. His body was left in the courtyard in hopes Alyssa would claim it. She did not. 

While hiding across the Narrow Sea, Alyssa's eldest  daughter was forced to marry her uncle Maegor, becoming one of his 'Black Brides'. She returned to Westeros with her only surviving son and youngest daughter, being welcomed in Storm's End in 48 AC. There, Rogar Baratheon, the first to claim his support, proclaimed her youngest son Jaehaerys as king. Alyssa stood beside her son as he vowed to end Maegor's reign. Nine days after Maegor's death, Jaehaerys returned with his mother and sister to King's Landing to claim the throne; Alyssa arrived a fortnight later with Lord Rogar and a large host.

During the minority of her son, Jaehaerys I, Alyssa served as his regent. She accompanied her son to Oldtown where he reconciled the crown and the faith, and there it is said either she or her daughter switched her grandaughters, Aerea and Rhaella. Her regency was marked by strife however, as her eldest daughter Rhaena married without informing or inviting her mother, the start of a rift between the two that would only be mended with the dowager queen's death. Later that year, Alyssa married the Hand of the King and her son's long time supporter, Rogar Baratheon, in what would come to be known as the Golden Wedding. 

Following this came an argument as to the bride of the young king. A difficult matter, Alyssa knew as well as any that her son would choose his sister, Alysanne. Fearing a repeat of the unrest caused by the marriage of her two eldest children, Alyssa greatly protested. As a result, Aegon and Alysanne stole away to Dragonstone, much to the chagrin of both the queen regent and the hand. When Rogar suggested setting aside the crown to Rhaena's eldest daugher, Aerea, Alyssa stripped him of positions and sent him back to Storm's End, snuffing out any affection the pair had. Alyssa sent a raven to her son informing him of his decision and then named her brother, Daemon Velaryon, as new Hand of the King. Afterwards, she retired from ruling for the rest of her son's minority.

Having reconciled with her two younger children and her husband upon Jaehaerys's ascent to the throne, it came was a surprise to everyone when Alyssa became pregnant once more. She gave birth to her second husband's first son, Boremund, in 52 AC. She never truly recovered however. She became pregnant once more in 54 AC, going into labor a month early. At the brink of death, her husband Boremund gave consent to Maester Kyrie to cut his wife open in order to save his child, a girl named Jocelyn. She died shortly after, and with her death her daughter Rhaena cursed the Lord of Storm's End.