Once the holds were filled, the two ships, the Trinidad and the Victoria, took advantage of the winter monsoon whose winds would carry them towards Africa. However, shortly after setting sail, the Trinidad started taking on water.

Juan Sebastián did not postpone his departure and on the 21st of December he gave orders to set sail.

Several weeks after the Victoria disappeared over the horizon, a messenger left the island of Ternate with a letter written in Malay for the king of Portugal, warning of the imminent arrival of the Spanish. The Portuguese captain Antonio de Brito, who arrived later on Tidore, wrote to Lisbon that it would be "a miracle" if the Victoria were to get to Spain.

The cabin boys Martín de Ayamonte and Bartolomé de Saldaña abandoned ship on the island of Timor. They told the Portuguese captain who later cpatured them that the Victoria was taking on a lot of water and that, in defiance of his officials, Juan Sebastián refused to sail into Maluku where the Portuguese were.

On the 18th March they came across an uncharted island but as they could find nowhere to drop anchor, they continued on their way. This island would have to wait for a whole century before its new discoverer would name it: the Island of New Amsterdam.

On the 13th April they passed the 40th Parallel South. Habituated as they were to life in the tropics, the extreme cold came as a shock. On the 8th May they saw land and thought they had passed the Cape, but in reality they still had another 800 kilometres to go.

On May 16th a mast broke, but in spite of this, four days later their log confirms they had left behind the mythical Cape.

The rising death toll from scurvy finally forced Juan Sebastián's hand and on the 1st July he called his men together and they voted in favour of stopping at the island of Santiago, Cape Verde. The Victoria dropped anchor some way away from the harbour and a rowing boat went ashore with the scribe Méndez in charge. They had invented a story so that the Portuguese wouldn't know where they had come from, and to begin with they were welcomed warmly. However, they soon realised that the story was missing a day, which the Spanish could not account for, and on the rowing boat's third crossing the Portuguese became suspicious and held the thirteen men aboard the boat.

Juan Sebastián was ordered to give himself up, but instead he gave orders to weigh anchor. At the very least, the fresh food they had brought on board was enough to stave off scurvy for those left on the ship.

Currents and winds pushed them inexorably north-east until, on the 20th August, they reached 42º 36', which brought them nearly level with Finisterre. From there onwards the winds blew fair and two weeks later, on the 4th September, they sighted Cape San Vicente. The eighteen survivors didn't take their eyes off land until they moored in Sanlúcar. On arrival, Juan Sebastián wrote to the Emperor, giving him a brief description of the voyage.

The original letter was lost, but three centuries later copies were discovered in different European cities. We can see these numbered 42
.
It is very interesting to see the collective vision the captain showed in the brief description of his journey:

There are some differences between the copies and we have made a compilation of all five. If you'd like to listen, press 42.1

Your Highness and most illustrious Majesty: Your Majesty must know that eight and ten men have returned, safe and sound, with one of the five ships which Your Highness sent to discover spices, under the charge of captain Fernando de Magellan, may he rest in peace; and to explain the principal things we have discovered on our journey, I briefly set them here for Your Highness to read:

Firstly, we sailed to 54º south of the Equator where we found Straits, ten leagues long and passing through Your Highness' lands and emerging in the Indian Ocean. In three months and twenty days we came upon no land, and only two small, uninhabited islands, followed by am archipelago of many islands which had much gold. The death of our captain, Fernando de Magallanes, and of many other men left us with few hands and unable to sail the ships, so we dismantled one, and with the remaining two we sailed from island to island, arriving, with God's help, at the islands of Maluku, eight months after the death of Fernando de Magallanes, and there we loaded the two ships with cloves.

Your Majesty must know that, sailing for those islands of Maluku, we discovered camphor, cinnamon and pearls. We wished to leave Maluku and return to Spain, but discovered that one of the ships was taking on water at a terrible rate and we would have to unload everything in order to repair her. The season for sailing for Java and Maluku was coming to a close, so we resolved to serve our King or die in the attempt to relay news of our discovery, and leave in one sole ship, in a sorry state and arriving only God knows how. On our voyage, we discovered many wealthy islands, including Bandam, where ginger and nutmeg grow, Java where pepper is cultivated and Timor which produces sandalwood, not to mention a plentiful supply of ginger as on all these islands. I bring samples of all this produce, collected from the islands where they grew, to show Your Majesty. I also bring wishes of peace and friendship from the kings and lords of these islands, signed in their own hand and desiring to serve and obey You as their natural King and Lord.

All of these islands are on the boundary of the demarcation resulting from the conquest, as our letter and explanation clearly and truthfully relates to Your Highness and all-powerful Majesty.

Having left the last of these islands, and having eaten nothing but rice for five months, and drinking only water, we landed nowhere, for fear of the king of Portugal who had ordered all his men to take our fleet so that Your Majesty might hear nothing of us; and because of this, twenty-two of our men died of hunger. This lack of victuals forced us to drop anchor at the island of Cape Verde where the Governor captured our boat with thirteen men aboard and wanted to take me and my men in a ship sailing from Calicut to Portugal and filled with spices, saying that only the King of Portugal could traffic in spices, and arming four ships to capture us.

But we all agreed that we should die before falling into the hands of the Portuguese, and thus, with great effort and working the pumps day and night, we bailed water for all we were worth and, with the help of God and Our Lady, after three years we have come home.

I therefore beg Your Majesty to secure from the King of Portugal the freedom of those thirteen men who have served You for so long. Your Majesty must know that the most important thing to take into account is that we have discovered and followed a way around the whole roundness of the world, leaving towards the west and returning from the east.

I beg Your Majesty, for the effort, sweat, hunger and thirst, cold and heat that the men in your service have suffered, you pay them with 150 quintals and the fourth and twentieth of what they have returned with. And here I close and kiss the hands and feet our Your Royal Highness.

Written on board the Victoria, in Sanlúcar, on the sixth day of September, 1522 . — Captain Juan Sebastián del Cano.