Monaco routed Ligue 2 side Lens 6-0 at home, while Guingamp scored late to edge fourth-tier Cannes 2-0 away from home.
At the Stade Louis II, hosts Monaco opened the scoring in controversial fashion, as Lucas Ocampos deflected Fabinho's goal-bound shot into the net from an offside position in the 17th minute.
The flag stayed down despite no Lens defender putting Ocampos onside as the Argentine slid over the goalline as he got the final touch.
Monaco's lead was doubled by Dimitar Berbatov, via a one-two with strike partner Emmanuel Riviere four minutes out from half-time.
Berbatov played a ball wide for Riviere, whose cut-back pass found the former Manchester United man in the box, who finished clinically.
The floodgates opened in the second half, as Claudio Ranieri's men scored three times in a 13-minute period.
Riviere, Fabinho and Ocampos all found the back of the net to pile the misery onto Lens.
Provider for Berbatov's goal, Riviere was repaid the favour by the Bulgarian, who put through his team-mate after some class one-two passing, and the Frenchman finished off under pressure from Lens' scrambling defence.
In the 58th minute, Monaco's lead grew, as Fabinho had time to take a touch from Nicolas Isimat-Mirin's set-piece before the Brazilian lashed home the hosts' fourth goal from the back post.
Ocampos earned a brace on 67 minutes, sneaking in at the far post from Nabil Dirar's low cross, and wrong footing Lens goalkeeper Rudy Riou to net Monaco's fifth.
The cherry on top of Monaco's win was an own goal to Lens defender Loic Landre, who got the final touch into his own net from an Ocampos cross on 85 minutes.
Guingamp had a much tougher time of progressing into the final four but a late double to Mustapha Yatabare saw them past amateur club Cannes.
The Stade Pierre de Coubertin hosts were down to 10 when left-back Lucas Rouabah was dismissed seven minutes prior to half-time.
However, Guingamp kept their sheet clean until the 71st minute, when Yatabare struck - duly assisted by Fatih Atik - before the Malian striker added his second 12 minutes later.
The result ended Cannes' giant-killing run in the cup, which saw them oust Saint-Etienne and Montpellier on their way to the last eight.
‘After Manchester City’s recent form, maybe they’re the underdogs against Manchester United!’ Former Red Devils defender on this weekend’s derby
‘Arteta, Alonso, Emery, me… none of us were physical players – we needed the understanding of the game. That probably helped us move into management’: Premier League boss reveals reasons for natural career progression
