The 62-year old Welshman, one of the most experienced managers still working in British football, succeeds Garry Monk, who was sacked by the Yorkshire club earlier this week.
Pulis, whose career includes stints in charge of Stoke City, Crystal Palace and West Bromwich Albion, returns to management after leaving Middlesbrough in May 2019 – a club where he also replaced Monk.
He arrives at Hillsborough with Wednesday second-bottom in English football's second tier.
The Owls were hit with a 12-point deduction for the 2020-2021 season in July after being found guilty of breaching profitability and sustainability rules, before the punishment was reduced to six points last week after an appeal.
A run of four straight defeats ended with a 1-0 win against Bournemouth before Sunday's (AEDT) goalless draw with Millwall proved to be Monk's last game in charge.
Pulis, who oversaw Stoke's promotion to the Premier League in 2008, is set to take charge of his first Wednesday game when the Owls travel to Preston North End a week on Sunday (AEDT).