This prize yielded the greatest English plunder of the century, including five hundred tons of spices, silks, gemstones, and other treasures.

An attempt to raid Spanish Jamaica in January 1603 ended in failure, after being repelled by militia under the command of Governor Fernando Melgarejo.

The company had been granted a proprietorship to establish a settlement in the Virginia Colony by King James I. Newport took charge of the ship Susan Constant, and on the 1606–1607 voyage, she carried 71 colonists, all male, one of whom was John Smith.

As soon as land was in sight, sealed orders from the Virginia Company were opened which named Newport as a member of the governing Council of the Colony.

On 29 April, Newport erected a cross at the mouth of the bay, at a place they named Cape Henry, to claim the land for the Crown.

In the following days, the ships ventured inland upstream along the James River seeking a suitable location for their settlement as defined in their orders.

Despite original intentions to grow food and trade with the Native Americans, the barely surviving colonists became dependent upon the supply missions.

However, despite replenishing the supplies, the two ships also brought an additional 120 men, so with the survivors of the initial group, there were now 158 colonists, as recorded later by John Smith.

Normally, ships destined for North America from Europe sailed south as far as the Canary Islands as at that latitude the mean direction of the wind is to the West, pushing them across the Atlantic (ships returning to Europe turned eastward at the Carolinas, as at that latitude the mean wind direction is to the East), then followed the chain of west Indian islands to Florida and from there followed the Atlantic coast of the continent.

Eventually, in May 1610, the survivors (150 colonists and crew members, and one dog) constructed two smaller ships, the Deliverance and the Patience, from the wreck and the abundant native Bermuda cedar.

Arriving at Jamestown 10 months later than planned, where the death of over 80% of the colonists had occurred during the Starving Time, Newport and the others had precious few supplies to share.

However, as they approached Mulberry Island, they were met by a 'fourth" supply mission sailing upstream headed by a new governor, Thomas West, who ordered the remaining settlers to return.

[citation needed] On 12 May 1611 Newport arrived once again back at Jamestown, accompanied by Sir Thomas Dale, departing 20 August, for what would be his last time.

In November 1616 he wrote his will, and set out on his third voyage to the East Indies (this time accompanied by his son, also called Christopher, who joined the crew).