The Reds were paired with the Portuguese club during Monday morning’s draw for the first round of the knockout stage, at UEFA headquarters in Switzerland.
Jürgen Klopp’s side earned their place in the pot as a seeded team after claiming top spot in Group E, ahead of Sevilla, Spartak Moscow and NK Maribor.
The first leg of the last-16 tie will be held at the Estadio do Dragao, with the return to take place at Anfield.
Liverpool and Porto have met four times competitively, with the most recent encounter coming in the 2007-08 Champions League group stages.
After a 1-1 tie in Portugal, the Reds recorded an emphatic 4-1 victory in the return meeting at Anfield.
The sides also went head-to-head in Liverpool’s run to UEFA Cup success in 2001, with Gerard Houllier’s team earning a goalless draw in the award leg before winning 2-0 at home in the fifth-round clash.
For details on when the two fixtures will be played, click here.