The movie actually opens near the end of the move events. Dr Juvenal (Benjamin Bratt) is very old. He climbs a ladder to feed a bird and falls off and dies.
Cut to an old Florentino (Javier Bardem), he is in bed with a very young woman and they hear church bells. He jumps out of bed and makes the statement that “someone important has died’. He quickly dismisses the woman and heads off to the church.
There we see him interface briefly with Fermina (Giovanna Mezzogiorno) who is grieving and he introduces himself, which enrages Fermina.
Cut to about 50 years earlier and we see the goings on of the town and the problems of the Cholera epidemic. We're introduced to a few more characters like Florentino’s uncle who runs boats, both a younger Florentina (Unax Ugalde) and Fermina as well as Fermina’s father (John Leguizamo).
Florentino is a lowly worker and during this time is smitten just by looking at Fermina.
What ensues is some secret letter passing and building of the relationship in which Florentino expresses his fidelity and devotion to Fermina who at first is hesitant but at the end is overtaken by Florentino. We see some scenes which show some serenading and some additional, albeit fairly weak building of the relationship.
Fermina's father finds out about her relationship with Florentino and freaks out stating basically that she is to good for a lowly worker like him…they end up actually packing up and moving away because of this; to the extreme despair of Florentino.
We see Fermina fall sick with the fear of it being Cholera, I cannot remember if they move back before this or because of this but at any rate
We are introduced to a young Dr Juvenal, (still Bratt) who comes in to examine Fermina and is also smitten by her. She does not have Cholera…later he revisits her by surprise and Fermina’s father is all happy with the Dr. and basically promotes a relationship. Fermina and Florentino do see each other again and she basically dismisses him…Fermina and the Dr. end up getting married and have a couple kids.
So at this point Florentino is basically grief stricken and basically cannot function and his mother tries to snap him out of it. She has him sent far away to work for his uncle so he can take his mind off of Fermina. At one point he is on a boat and he is grabbed and essentially raped by a woman (who apparently do this for fun).
He has an epiphany basically and realizes that he can only deal with his grief over losing Fermina by being with other woman…. so we see some history of his escapades and his diary of how these happen. He is getting over fermina…. but...
He does come back home to be with his mother who is getting senile (eventually dies). He sees Fermina here and there around town; they are 20-30 yrs older now though. And he has his feelings rekindled.
He continues his sleeping around with the story also showing a pretty bad marriage of the Dr and Fermina with the Dr also cheating on her and she leaves him and goes away for a while. (One of the women he sleeps with ends up getting killed by the husband who found out).
More Florentino escapades in which he describes being up to 400 - 500 women, eventually 622 women documented.
Fermina and the Dr. do get back together through some other scenes and then we revert back to 50 plus year later and the Dr. dying and we are back at the funeral where the movie started.
After 53 yrs and some days Florentino expresses his love still for Fermina who is insulted after all this time. Florentino writes letter after letter and eventually Fermina is won back over much to the disgust of her kids.
After some time rekindling they end up going on one of the boats that he now owns due to his uncle being dead.
On that trip, he finally sleeps with Fermina………….after getting off the boat, he waits until the boat is empty then has the captain take them by themselves out again where they anchor in the sunset.