This opening line explains that Paradise Lost will focus on the Genesis story of Adam and Eve and their fall from grace. "Man's first disobedience" was eating the fruit (described as an apple in Paradise Lost) of the tree of knowledge of good and evil, the one act God forbade them. Created immortal, by tasting it they are made mortal, meaning that they will die, as will all their descendants. Eating this fruit not only brings "Death into the World" but also "all our woe" or misery because God expels Adam and Eve from paradise. After this act, they will have to work hard and suffer to survive, as will their descendants.

Milton's introduction to his epic offers us, like the overture to a symphony, a taste of what is to come. This is important for orienting the reader. The poem starts after God and his angels have defeated Satan and his demons in a war in heaven. Satan, in hell, makes the decision to try to get vengeance on God by hurting the crowning glory of his creation, humankind. It will not be until book 9 of the poem, however, that Satan makes a successful entry into the garden and is able to deceive Eve into eating the apple.

Milton starts off his great epic poem by telling us what its theme is going to be. "Man's first disobedience" refers to Adam and Eve's act of eating from the Tree of Knowledge, in express defiance of God's explicit command. That's what Milton is referring to by "the Fruit / Of that Forbidden Tree."

Adam and Eve were tricked into eating the forbidden fruit by Satan in the guise of a serpent. But in doing so, they sinned and, as Milton tells us in the first few lines of the poem, "Brought Death into the World and all our woe." Before Adam and Eve ate the forbidden fruit, the Earth was a genuine paradise without death or sin. But ever since they succumbed to temptation and defied God, the Earth has been wracked by all manner of calamities. All of us have inherited Adam and Eve's sin—their original sin—and the whole of humankind has been paying the price ever since.

These lines at the beginning of the poem Paradise Lost by John Milton comprise a summary of the Biblical story that the poet is telling: an account of Adam and Eve in the Garden of Eden, Satan's temptation, and the fall of man. It serves as an introduction to the poem that is to follow. You can find this account in chapters 2 and 3 of the book of Genesis in the Bible.

"Man's first disobedience" refers to the first time that Adam and Eve deliberately go against God's commandment. This has to do with "the fruit of that forbidden tree." When God creates Adam in the garden, he tells him that he can eat anything he finds there except the fruit from the tree of knowledge of good and evil. God warns Adam that if he eats from that tree, he will die.

God then creates Eve, and evidently Adam has told Eve what God said, because when Satan talks to her, she is aware of the restriction against eating from that one tree. However, Satan tempts her to eat it, and she does, and then she coaxes Adam to eat it as well. This is the fruit "whose mortal taste brought death into the world, and all our woe." In other words, because Adam and Eve taste the fruit from the tree of the knowledge of good and evil, they become disobedient, something that has never happened before. As a result, God keeps his word and drives them out of the Garden of Eden, which is like paradise, and into the world outside, where they have to work hard, suffer, and eventually die.

John Milton opens Paradise Lost with "The Argument," a short summary of the Book; these lines describe Man's fall into sin after Eve and Adam eat from the Tree of Forbidden Fruit. Their having eaten from this tree has caused death and sin to come into the world, and "Man" is cast out of the Garden of Eden to have to struggle for existence. 

These lines which begin the first book of Paradise Lost allude to man's sin of disobedience in the Garden of Eden when Eve first ate from the tree that God forbade them to eat its fruit. In the first line "Fruit" is a pun upon the apple that Eve and Adam eat and the figurative "fruits" of their actions. After Adam and Eve are driven from Eden, it is not until "one greater Man," Jesus Christ, comes that mankind is "restored."

Paradise Lost addresses the question of how man [humanity] can endure in a fallen world, and it justifies the ways of God to Man. The first Book proposes the entire subject of Milton's renowned Poem written in English Heroic Verse without rhyme. This Book touches upon the cause of the Fall (as the lines above exemplify), Satan in the form of the Serpent who tempts Eve as he is "Stirr'd up with Envy and Revenge," Satan's revolt from God, and his having been driven from Heaven with all the others. Interestingly, in the European cultures, it is rather often that many people's beliefs in the history of Creation and Satan's existence derive from Paradise Lost and are confused with passages from the Bible.