As Isaac nears death, he prepares to give Esau a blessing, but Rebekah conspires with Jacob to take this blessing by dressing him in Esau's clothes. Jacob gives Isaac food and wine, and Isaac blesses him. When he learns of the deception, he will not take back his blessing, as it has already been spoken, and he tells Esau that he will serve his brother, but that eventually he will break free.

Jacob flees from Esau up to Haran and Esau takes Mahalath, Ishmael's daughter, as a wife. While Jacob is traveling, he has a vision of angels going up and down a ladder from Heaven to earth. In this place, Jacob promises to give God a tenth of everything if God will watch over him.

Jacob travels to Laban, and serves him, and when Laban offers him payment, he asks for Laban's daughter, Rachel in marriage, but Laban gives him his other daughter, Leah, and Jacob is convinced to work longer for Laban for Rachel. Seeing that Jacob preferred Rachel, God opened Leah's womb and she gave Jacob many children, but Jacob still preferred Rachel, and both wives try to give Jacob more children.

Isaac prayed that his wife Rebekah have a child, and she had twins, Esau and Jacob. Jacob was born grasping Esau's heel, which is prophetic given how he would later contend with God, and references to this can be seen in Hosea 12 and Micah 1. Jacob convinces Esau to give away his birthright in a moment of hunger.

When a famine fell upon the land, Jacob went to Gerar, and Abimelech, the king. God told Isaac not to journey to Egypt, so he remained in Gerar. Isaac became rich, and Abimelech sent him away.

Sarah dies and Abraham makes a contract with the Hittites to purchase a plot of land to bury Sarah. Nearing the end of his life, Abraham instructs his servant that Isaac must not take a Canaanite wife, but rather a wife from Abraham's country. When he has done this, Isaac must settle in the land of Canaan, which God has promised for him.

The servant prays that God might give a sign identifying the woman to choose for Isaac's wife, that she might offer water to both him and his camels. This woman is Rebekah, and she hastens to Isaac in the Canaan land, and they are married.

Abraham marries Keturah after Sarah's death, and has more children, but his heir remains Isaac.

Lot leaves Zoar, and his daughters wanted to have children, so they got Lot drunk so that they might get pregnant by him, and through Lot they bear Moab and Ben-ammi, the origin of the Moabites and Ammonites.

Abraham goes to Gerar, where he encounters Abimelech. Abimelech, not knowing that Sarah is married, wants to add her to his harem, but God, wishing to preserve the lineage of Isaac, tells Abimelech in a dream that she is married and he confronts Abraham and Sarah and sends them away with gifts. Abimelech later comes to Abraham and asks that Abraham might remember his kindness with his descendants when Abraham comes into power.

Sarah names her son Isaac, for laughter, and when she sees Isaac with Ishmael, his older half-brother, she sends Ishmael and Hagar away, but an angel of the lord tells Hagar that Ishmael will also be a great nation.

God tests Abraham and asks him to sacrifice his son, but before he can do it, an angel stops Abraham, and God blesses him for not holding anything back. Gal 3:15ff points out that the promises to Abraham were made to him and his offspring, singular, meaning Christ. The sacrifice of Isaac also is a precursor of the willing sacrifice of Christ, and of the resurrection (for if Isaac had died, God would have to have raised him to fulfill his promises).