Goals from Diego Milito, Kenya midfielder McDonald Mariga and Cristian Chivu saw the champions claim three vital points in the title race after Simone Tiribocchi's opener for the visitors on Saturday.
Inter now lead Roma by two points although the capital based club can return to the summit if they beat Sampdoria at Rome's Stadio Olimpico today. Atalanta remain in the bottom three, two points from safety.
The win allowed Inter to put Mario Balotelli's shirt-throwing incident, against Barcelona in midweek, behind them although some fans demonstrated banners indicating they had not forgotten his petulant antics.
It was the second week in a row in which Inter played before Roma and once again they managed to heap maximum pressure on their rivals.But following their Champions League exertions in midweek, coach Jose Mourinho rang the changes, with four of Tuesday's starters on the bench and two left out altogether.
Those who came in took time to settle down and it was one of them who was at fault for Atalanta's fifth-minute opener.
Thomas Manfredini played a long ball forward from left-back and World Cup winner Marco Materazzi was ill-advised in pushing up, trying to catch Tiribocchi offside, he failed and the forward buried a rasping drive from the edge of the box.
Inter, though, gradually found their stride and took control but it was another mistake on 24 minutes that allowed them to equalise. Wesley Sneijder hit a ball over the top on the counter-attack but it was heading straight for Paolo Bianco who should easily have cut it out.
Instead it skipped off his thigh and Milito ran onto it before flicking a delightful lob over Ferdinando Coppola from outside the area with the goalkeeper in no-man's land.
Inter took the lead 10 minutes before the break as Sneijder fed Samuel Eto'o on the left before missing his centre, only for Mariga to pop up behind him and drill home from 10 yards.
The hosts threatened to put the game to bed before half time but Ivan Cordoba's header was straight at Coppola and Eto'o blazed high over the bar at the back post on the volley.Atalanta started the second half brightly with Tiberio Guarente firing just over from distance before Julio Cesar tipped over a Manfredini free-kick.
Midway through the second period Inter looked certain to score on the counter but Coppola stuck out a boot to block Muntari Sulley's fierce shot from 20 yards, when teed up by Milito.
A quarter of an hour before the end substitute Thiago Motta brought a sprawling save out of Coppola with an acrobatic volley from the edge of the area.Then 12 minutes from time Chivu made the points safe as he was given time and space to hit a rocket from distance in off the post.That allowed Mourinho to use his substitutes to ensure as many players as possible got some rest ahead of Wednesday's trip to Spain