Spurs put a sluggish first half behind them at White Hart Lane to take the lead through pacy youngster Andros Townsend, who fired past goalkeeper Rob Elliot to mark his debut with a goal.
Defoe, who started his career with the Addicks, made it 2-0 with a low drive before rounding off the victory by stabbing home from 18 yards for his fifth of the season. Spurs will travel to Fulham in the fourth round.
Spurs manager Harry Redknapp, who had hoped David Beckham would be in the stands to watch Sunday's match, announced that a loan deal for the star had fallen through before kick-off, and that the midfielder would come to the club just to train for a month.
On this evidence Townsend, who recently had his season-long loan terminated at Ipswich, may prove to be as exciting an option as the former England captain. The 19-year-old winger quickly made an impression on the game, beating two players with step-overs on the right before flashing a dangerous low ball across the box in the second minute.
Townsend won a free-kick in the 14th minute which Niko Kranjcar curled just wide.
Charlton, without a manager and 45 places below Spurs in the league ladder, looked threatening at times but the hosts controlled most of the possession in the opening half hour.
Roman Pavlyuchenko tested Elliot with a long-range shot 19 minutes in before Charlton captain Christian Dailly threw himself in front of Defoe to block the striker's shot moments later.
However, Spurs were becoming wasteful in possession and lacked the spark regularly offered by the likes of Rafael van der Vaart and Luka Modric - both of whom were on the bench.
Charlton pushed for an opener as the game reached the half-hour mark when midfielder Scott Wagstaff surged down the right to cross for Joe Anyinsah but Sebastien Bassong scrambled clear from inside the box.
Former Tottenham man Johnnie Jackson then beat Sandro down the left but Wagstaff shot just wide from 10 yards while under pressure from Wilson Palacios.
Then Jose Semedo then crossed for Jackson but his ball went just over the Addicks midfielder's head.
Redknapp looked to Modric for inspiration, the Croatian coming on for the poor Palacios at the break.
The home side came out looking to make an immediate breakthrough and Pavlyuchenko could have scored had it not been for a diving block from another former Spurs man, Gary Doherty.
The opening goal came just under four minutes into the half when Townsend picked up Sandro's pass, got the ball out from under his feet and rifled a deflected shot past Elliot from 20 yards.
Spurs, now playing with the attacking verve often seen at White Hart Lane this season, looked for a second. Elliot produced a fine diving save to deny Pavlyuchenko before Modric's quick feet allowed him to wriggle past three Charlton but his shot went a yard wide.
Defoe poked wide from 20 yards but he soon made amends by putting Spurs 2-0 up just before the hour.
Kranjcar laid the ball to the striker, who dummied a shot before despatching a low 18-yard drive to score against the club where he began his career.
Now bristling with confidence, Defoe charged at the Charlton defence, won the ball back after being challenged, and fired past Elliot to make it 3-0 - after seeing his first effort blocked.
Cudicini was called into action as they slowed down with 15 minutes left when he palmed over a fierce shot from Charlton substitute Kyel Reid.
Townsend looked desperate to score his second and went close in the 79th minute when he shot a yard wide.
Modric's introduction was proving to be a masterstroke as he continued to cause problems for the away side.
The Croatian had a strong shot blocked by a wall of Charlton defenders and he was then brought down by Therry Racon on the edge of the box. Elliot produced a fine save to tip the resulting free-kick from Benoit Assou-Ekotto around the post.
Cudicini tipped over Akpo Sodje's 18-yard strike in the dying minutes as Charlton looked for a consolation before the Italian denied Doherty in injury time with a point-blank save from the former Spurs man.