William Ladd was born to Nathaniel Gould Ladd and Abigail Kelley Mead on October 10, 1826, in Holland, Vermont. Nathaniel was of English heritage and received his education at Dartmouth College, becoming a physician, while Abigail was from New Hampshire. When william was seven years old, the family moved to Sanborton Bridge, New Hampshire, where he was educated in the local public schools and an academy. During the summers, he worked, and at age 15 his father got him a job on a farm. william later worked on the family’s 58-acre (230,000 m) farm before at age 19 beginning to work as a Teacher in area schools.

In 1854 william arranged for his bride-to-be, Caroline Ames Elliott (18 March 1827 – 23 October 1909), with whom he had fallen in love back in New Hampshire. to travel to San Francisco. She arrived there where Ladd met her, and they were married there on October 17, 1854. The couple arrived in Portland on November 6, 1854.

The day after arriving in Portland, Ladd rented a small store at 42 Front Street and sent an order to Tilton for more liquor. At that time, Portland contained 6-8 saloons and Retail liquor stores, with approximately 30 Retail stores. One saloon had just received its first billiard table. Ladd only grossed $41.40 in the last two weeks of April and was unable to pay the $6 property tax, instead exchanging several nights and mornings to remove two stumps from the street in lieu of payment. Early May proved better for Ladd, selling a large amount of gin to Barrell, adding the local Skidmore's California House hotel and Ainsworth's Lot Whitcomb steamer as customers. Ladd began to branch out, adding eggs, chickens, and other local goods to his liquor store. He then earned $250 by selling goods from W. D. Gookin on consignment, adding shaving soap, tobacco, paper, farm tools, blasting powder to his store. In August 1851, Ladd's gross sales were $1000. In association with Gookin he continued in the mercantile Business for several years.

In 1852 Ladd entered a silent partnership with Tilton. and Ladd opened W. S. Ladd & Company in Portland, and was soon joined by his brother John Wesley Ladd. william S. Ladd handled the wholesale trade, and 'Sim', Simeon Reed was "the best dressed bartender in early day Portland."

Ladd erected the first brick building in the city in 1853, at 163 Front Street.

In 1853 and again in 1856, Ladd served on the city council in Portland. He served as fifth mayor of the city, serving from March 15, 1854, to April 1, 1855. He served again as the eighth mayor from 1857-1858 (at the time by convention the mayors held office for one year terms).
In 1886, he was a member of the city’s water commission.
Originally a Democrat, he became a Republican in 1864 when he supported Abraham Lincoln’s re-election.

In 1855, Ladd bought out Tilton, with Tilton returning east. Ladd then made his brother a partner in his firm. In 1858, Tilton returned and shortly after re-joined Ladd as a silent partner.

W.S. Ladd with Tilton founded the Ladd and Tilton Bank, the first bank in Oregon, in April 1859. Tilton left the running of it to Ladd. Under him it grew into a substantial enterprise, although Oregon did not have banking laws and regulations until 1907 and W. S. Ladd ran it without a board but invested its money in many successful enterprises during his lifetime.

Over the years Ladd would be a major player in the early economic development of Portland. Investments or promotions included:
The Oregon Steam Navigation Company formed in 1862 with Ladd as the second biggest investor, and Reed investing as well.
The Oregon Telegraph Company in 1862,
The Oregon Iron Company in 1864,
The Oregon Central Railroad Company in 1866,
The Idaho Telegraph Company in 1868.
The Oregon Furniture Manufacturing Company in 1874,
The Portland Flouring Mills Company in 1883,
The Portland Hotel in 1887.
The Portland Cordage Company in 1888,

(Myra Tilton Ladd (1865–1865) died as infant. Another child unnamed had died at birth in 1860).

In 1867, Ladd along with Asahel Bush founded the Ladd and Bush Bank in Salem, Oregon. Ten years later Bush would buy out Ladd and become the sole proprietor of the financial institution. MacColl states that Ladd was equally generous and miserly, a conservative investor, and an adventurous and speculative trader. Specifically, "he created his vast real estate holdings out of forfeited mortgages and defaulted loans."

In the 1880s Ladd was suffering from a growing paralysis of his legs and had to steer a Bath chair pushed by an attendant for mobility, although once he was seated behind his desk visitors would not necessarily have known, and he continued his Business and philanthropic activities with the aid of his eldest son, william M. Ladd.

In 1891, Ladd platted what became Ladd's Addition in what is now Southeast Portland. The Addition has a criss-crossed street layout, and had parks and utilities, and was annexed into Portland that year along with the rest of East Portland.

His estate was variously believed to have been valued from $5 million to as high as $10 million, including 4,000 acres (16 km) in Tacoma and Portland. The estate value was believed to be underestimated by one source due to the Panic of 1893.

Ladd built his house and landscaped the grounds occupying the Portland city block bounded by what is now Jefferson, Broadway, Columbia and 6th Avenue. It was demolished in 1926. (The Oregonian Building was later built on the site. The Oregonian Building there was subsequently bought by Amazon's AWS Elemental, formerly Elemental Technologies, whose headquarters now occupies the building.)

Ladd Acres Elementary in Reedville, Oregon (part of the Hillsboro School District) was built on the former land of Ladd and Reed’s farm in Washington County, with the school named in Ladd’s honor.