The first flight took off from Stansted on Wednesday (11 May) at 11:35am. Flights from the London airport operate four times a week with prices from £199pp.
After launching its transatlantic service to Baltimore/Washington airport in April, the inaugural flight to Boston marks the second phase of Play’s transatlantic growth.
The icelandic carrier has seen its strongest bookings in recent weeks with 37,000 passengers in April, a 54% increase on March, and a load factor of 72.4% in April compared to 66.9% in March.
Chief executive Birgir Jonsson said the Boston expansion will support European travellers looking for "budget-friendly" access to the US.
"Around the world, tourists and holidaymakers are fuelling an international travel comeback," he continued. "As we continue to grow our presence in the US, we look forward to providing travellers with a no-frills approach to travel, where they can expect reliable yet affordable service from Play."