The Red-whites will start at home on 11 March. The second leg will be played at Ibrox in Glasgow a week later.
Slavia eliminated Leicester City in the Round of 32 with 2-0 away win after a goalless home draw. Rangers played a thrilling tie against Antwerp with 4-3 away win followed by 5-2 home victory.
Rangers are currently on top of the Scottish Premiership unbeaten in 30 league games 18 points ahead of Celtic. They have not lost a dingle game in the 2020/21 Europa League season eliminatin Lincoln Red Imps, Villem II and Galatasaray in the qualifying rounds and finishing on top of Group D ahead of Benfica, Standard de Liège and Lech Poznan.
This will be the first encounter of both clubs. Slavia played against St Mirren in 1985/86 and Hearts in 1992/93.