The Germany striker had not started in the league since September but wasted no time in showing his worth as Lazio ran riot in the first half at the Stadio Olimpico.
Having set up Stefano Mauri's opener on seven minutes, Klose netted his second goal of the campaign five minutes before the half hour.
Senad Lulic provided the assist for that goal, and the Bosnia and Herzegovina international was on hand a minute later to do the same, Klose making no mistake to fire past Alessio Cragno.
However, with Zdenek Zeman's half-time words for inspiration Cagliari pulled a goal back three minutes after the break, Edson Braafheid fumbling the ball into his own net in a goalmouth scramble.
Even after Victor Ibarbo had been sent off for the visitors they continued to pressurise Lazio, and when Joao Pedro fired home on 84 minutes it was the cue for a nervous end to the game for the hosts.
Those nerves were quickly settled, though, as Ederson converted an Andrea Candreva cross in stoppage time to seal Lazio's win, and lift them into third place in the table.
Meanwhile, Cesena moved level with Empoli on seven points after they were held to a 1-1 draw by Hellas Verona.
Pierpaulo Bisoli's side started the game brightly on Monday and took the lead on 22 minutes, Hugo Almeida's header playing in Gregoire Defrel who made no mistake.
They were unable to hold onto that lead, though, as Juan Gomez levelled for the visitors with 13 minutes to play.
Cesena pushed for a winner and thought they had got one in stoppage time but Emmanuel Cascione's header was superbly kept out by Rafael.
