The company said it will be moving into the former Wilko store on Westham Road.
The number of jobs that will be created has not yet been disclosed.
Wilko closed its doors for the final time in October 2023 after 24 years in the town, leaving many questioning what was next for the premises.
Weymouth has been dealt a number of blows to its high street in recent years with a number of businesses closing their doors – most recently being Cineworld which is shutting on December 30 – so the arrival of a big brand chain like Primark is being welcomed with open arms.
The company said it plans to open its doors at the site in early 2026, with works starting in the coming months.
At present its nearby stores are in Poole, Yeovil and Bournemouth.
Weymouth BID said it has been trying to encourage the company to open a site in Weymouth for a couple of years.
Some had hoped it would take over the large premises vacated by Debenhams in New Bond Street in 2021, but that became The Range.
Conor Walsh, Director of South West & North East at Primark:…